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Idigbe, Emmanuel Oni, Rosemary A. Audu, Edna O. Iroha, Adebola O. Akinsulie, Edamisan Olusoji Temiye, Veronica C. Ezeaka, Ifedayo M. O. Adetifa, Adesola Z. Musa, Joseph Onyewuche, and Sylvester U. Ikondu. "T-Lymphocyte Subsets in Apparently Healthy Nigerian Children." International Journal of Pediatrics 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/474380.
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Population studies showed that there are differences in T-lymphocytes subpopulation of normal children in different regions, and reference values in an area might be different from another. This study compared the values in our population with CDC and WHO reference values. Blood samples from 279 healthy, HIV-negative children<12 years of age were analysed for complete blood count, CD3+, CD4+, CD8+ counts and percentages. Except for CD8%, mean values for all parameters measured significantly decreased with age. CD4+ counts were higher in females than males,P<.05. Using the WHO criteria, 15.9% of subjects had low total lymphocyte count and 20.6% had low CD4 count. Children<3 years had median CD4% lower than WHO normal values. Our median CD4+ counts correlated with CDC values. Values used by WHO in infants are higher than ours. We suggest that our children be assessed using CDC reference values which correlate with ours.
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Chatila, T. A., and R. S. Geha. "Phosphorylation of T cell membrane proteins by activators of protein kinase C." Journal of Immunology 140, no. 12 (June 15, 1988): 4308–14. http://dx.doi.org/10.4049/jimmunol.140.12.4308.
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Abstract Activation of the enzyme protein kinase C (PKC) plays an important role in T cell activation. We investigated the phosphorylation of CD2, CD3, CD4, CD5, CD7, CD8, CD28 (Tp44), CD43 (sialophorin, gp115), and LFA-1 after incubation of human PBMC with the (PKC) activator PMA. These proteins were chosen for their role in transmembrane signal transduction (CD2, CD3, CD5, CD28, CD43), cell-cell interaction and adhesion (CD2, CD4, CD8, and LFA-1), or involvement in immunodeficiency states (CD43, CD7). CD5, CD7, CD43, and the alpha-chain of LFA-1 were found to be constitutively phosphorylated. PMA induced rapid hyperphosphorylation of CD5, CD7, and CD43, but not of the LFA-1 alpha-chain, and induced the phosphorylation of CD3, CD4, CD8 and of the LFA-1 beta-chain. PMA did not cause the phosphorylation of CD2 and CD28. PMA-induced phosphorylation was partially inhibited by the PKC inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride. Finally, the T cell activator Con A, which binds to the CD3/TCR complex was shown to induce a profile of protein phosphorylation similar to that observed with PMA. We conclude that PKC-mediated phosphorylation of T cell Ag may represent an important regulatory mechanism that governs the process of T cell activation.
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Raimondi, SC, FG Behm, PK Roberson, CH Pui, GK Rivera, SB Murphy, and DL Williams. "Cytogenetics of childhood T-cell leukemia." Blood 72, no. 5 (November 1, 1988): 1560–66. http://dx.doi.org/10.1182/blood.v72.5.1560.1560.
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Abstract The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes.
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Raimondi, SC, FG Behm, PK Roberson, CH Pui, GK Rivera, SB Murphy, and DL Williams. "Cytogenetics of childhood T-cell leukemia." Blood 72, no. 5 (November 1, 1988): 1560–66. http://dx.doi.org/10.1182/blood.v72.5.1560.bloodjournal7251560.
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The karyotypes of 57 cases of childhood T-cell acute lymphoblastic leukemia (ALL) were analyzed to establish the cytogenetic profile in this disease. Three questions were of particular interest. Do the chromosomal changes in T-cell ALL preferentially affect bands where genes encoding the T-cell receptor for antigen (TCR) have been mapped? Do alterations involving the TCR gene regions appear with any notable frequency in B-progenitor ALL? Do chromosomal abnormalities in this disease relate to stage of T-cell ontogeny? A relatively high proportion of cases (65%) had a pseudodiploid karyotype at presentation, the majority (58%) characterized by a translocation. The overall frequency of translocations was 44%, comparable to that among all banded cases of ALL seen in our laboratory. Hypodiploidy and hyperdiploidy were exceedingly rare (only four of 57 cases); 16 cases (28%) had apparently normal karyotypes. In half the cases with a translocation (14 of 24), the breakpoints were in regions to which the alpha and beta chain TCR genes have been mapped. Chromosomal breakpoints that were consistently observed in the vicinity of TCR gene loci were 7q32-q36 (TCR beta chain; n = 8), 14q11-q13 (TCR alpha chain; n = 6); other frequent breakpoints were 9p13-pter (n = 8) and 6q15-qter (n = 9). Chromosomal alterations occurred near TCR gene loci significantly more often in T-cell cases than in a comparison group of 335 patients with B-cell precursor ALL (26% v 1.5%, P = .0001). Stage I thymocyte development (CD7+, CD2+, CD5+, CD1-, CD3-, CD4-, CD8-) was noted in 23 cases, stage II (CD7+, CD2+, CD5+, CD1+, CD3-, CD4 +/-, CD8 +/-) in 25 cases, and stage III (CD9+, CD2+, CD1-, CD5+, CD3+, and either CD4+ or CD8+) in nine cases. The only statistically significant associations between cytogenetic findings and T-cell ontogeny were a higher frequency of normal karyotypes in cases with stage I thymocytes, and of pseudodiploidy in stage II cases. There was no apparent relationship between particular translocations and level of thymocyte maturation. Our findings indicate that most children with T-cell ALL have pseudodiploid karyotypes, although a surprisingly high percentage lack demonstrable abnormal clones. Specific chromosomal changes do not appear to be related to discrete stages of T-cell ontogeny as defined in this study, but they occur preferentially in bands containing TCR genes.
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Amalia, Fatya Alty, Arie Indra Gunawan, and Nono Wibisono. "Citra Destinasi Wisata Halal di Jepang: Wisatawan Dan Non-Wisatawan Muslim Dari Indonesia." Jurnal Bisnis dan Kewirausahaan 17, no. 1 (April 6, 2021): 1–10. http://dx.doi.org/10.31940/jbk.v17i1.2473.
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Wisata halal merupakan salah satu sektor bisnis halal yang masih berkembang karena banyaknya potensi wisatawan yang masih dapat dimanfaatkan lebih lanjut. Sebagai seorang wisatawan yang memiliki beberapa pilihan destinasi wisata halal, proses pengambilan keputusannya mengenai destinasi yang dipilih dapat sangat dipengaruhi oleh citra destinasi pada atribut wisata halal di destinasi tersebut. Penelitian ini bertujuan untuk mengkaji citra destinasi wisata halal di Jepang dari wisatawan dan non-wisatawan muslim Indonesia. Untuk pendataan dilakukan survey online (Mei-Juni 2020) terhadap umat Islam Indonesia dan menghasilkan 263 respon valid. Berdasarkan 12 atribut, 263 tanggapan tersebut dianalisis menggunakan uji Mann-Whitney U dan dilanjutkan untuk menguji ukuran efeknya. Hasil penelitian menunjukkan bahwa terdapat 3 dari 12 atribut (CD1, CD4, dan CD10) yang tidak berbeda nyata antara kelompok wisatawan dan non-wisatawan. Sedangkan atribut sisanya berbeda nyata antara kedua kelompok. Secara spesifik, gambaran CD3, CD5, dan CD12 pada wisatawan lebih kuat dibandingkan non-wisatawan. Di sisi lain, citra non-pengunjung dalam bentuk CD2, CD6, CD7, CD8, CD9, dan CD11 lebih kuat dari pada wisatawan. Berdasarkan temuan tersebut, Jepang sebaiknya menyesuaikan strategi promosinya berdasarkan sasarannya, baik wisatawan yang sudah memiliki pengalaman aktual maupun non-wisatawan yang hanya mengandalkan citra sekundernya.
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Park, Sang Chul, Tae-Gyun Kim, Hyung-Ju Cho, Chang-Hoon Kim, and Joo-Heon Yoon. "Reduced BDCA3+ dendritic cells in nasal mucosa induce severe inflammation in patients with allergic rhinitis and chronic rhinosinusitis." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 147.12. http://dx.doi.org/10.4049/jimmunol.204.supp.147.12.
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Abstract Dendritic cells (DCs) are specialized antigen-presenting cells that play a crucial role in T helper (Th) cell differentiation. DCs of human airway comprise conventional DCs (cDCs) and plasmacytoid DCs (pDCs), of which the cDCs lineage consists of cDC type 1 (cDC1) and cDC type 2 (cDC2). These DCs subsets differ in ontogeny and functional properties in immune response. Thus, we aimed to evaluate the expression of different dendritic cell subsets in nasal mucosa of patients with allergic rhinitis (AR) and chronic rhinosinusitis (CRS). Nasal polyp tissues or ethmoid mucosa from patients undergoing endoscopic sinus surgery or septoplasty were collected. The expression of DCs was investigated by flow cytometry via surface markers including BDCA-1 (CD1c) for cDC1, BDCA-3 (CD141) for cDC2, and BDCA-2 (CD303) for pDC. In subjects with AR, BDCA-3+cDC levels significantly decreased in patients with accompanying CRS, more reduced in eosinophilic CRS (ECRS) than in non-eosinophilic CRS (NECRS), compared to non-CRS patients. In subjects with CRS, the expression of BDCA-3+cDC decreased in patients with accompanying AR; more reduced in multiple allergens sensitization. Consequently, the IF result showed CD4+ CD25+ Foxp3+ regulatory T cell expression was significantly decreased in CRS patients with AR compared to those without AR. Furthermore, the level of BDCA-3+cDC was also inversely related with preoperative CT scores, serum eosinophils and IgE levels. We suggest that BDCA-3+cDC may play an essential role in immunoregulation and induction of clinical tolerance. Reduced frequency of BDCA-3+cDC followed by impaired Treg expression in CRS patients with AR might reflect the mechanism of severe inflammation in patients of CRS combined with AR.
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Takamatsu, Hiroyuki, Yoshihiro Yakushijin, Koji Miyazaki, Akiyoshi Takami, Masahide Yamazaki, Hirokazu Okumura, and Shinji Nakao. "C-Terminal Defect of CD20 on T-Cell Leukemia/Lymphoma Cells: Implications for Resistance to Rituximab." Blood 112, no. 11 (November 16, 2008): 5267. http://dx.doi.org/10.1182/blood.v112.11.5267.5267.
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Abstract Rituximab is commonly used for treatment of B-cell leukemia/lymphoma and its efficiency on CD20+ B-cell malignancies has been established. On the other hand, the effect of rituximab on CD20+ T cell leukemia/lymphoma is unclear. Two patients CD20+ T-cell malignancy (1 with T-cell prolymphocytic leukemia (T-PLL) and 1 with peripheral T-cell lymphoma, unspecified (PTCL-u)) were recently treated with rituximab without appreciable effects. The treatment failure prompted a study of the mechanisms underlying the resistance to rituximab therapy using leukemia/lymphoma cells of these patients and another CD20+ T-PLL patient. Patient 1: A 68-year old Japanese male was diagnosed as having T-PLL (small cell variant) characterized by CD2+CD3+CD4− CD5+CD8+CD20+TCR-Vβ8+. Southern blotting of these T-PLL cells showed a TCR-β gene rearrangement. The systemic lymphadenopathy and high-fever of the patient were ameliorated by the administration of prednisolone (20 mg/d). Rituximab was administered weekly, but no clinical improvement was observed. In vitro treatment of the T-PLL cells with rituximab did not show any complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Patient 2: A 75-year old Japanese male was diagnosed as having T-PLL (small cell variant) with a phenotype of CD2+CD3+CD4+CD5+CD8+CD20+. Southern blotting of these T-PLL cells showed a TCR-β gene rearrangement. The patient is being followed without treatment because his pancytopenia is non-progressive. Patient 3: A 67-year old Japanese male developed a left thigh tumor which proved to be PTCL-u. The phenotype of lymphoma cells was CD2+CD3−CD4−CD5−CD8+CD20+ and Southern blotting of these cells showed a TCR-β gene rearrangement. The patient’s PTCL-u was refractory to CHOP and rituximab plus EPOCH therapy. The reactivity of various monoclonal Abs specific to CD20 molecules against these patients’ leukemia/lymphoma cells is summarized in Table 1. CD20 molecules of these 3 patients’ leukemia/lymphoma cells were detectable by flow cytometry using anti-CD20 mAbs (L27 and rituximab) and also by Western blotting using anti-CD20 mAbs which recognize N-terminal region of CD20. However, the CD20 molecules could not be revealed either by immunohistochemistry using anti-CD20 mAbs (L26) or by Western blotting using anti-CD20 mAbs which recognize C-terminal region of CD20. The sequence of the full-length CD20 cDNA derived from Patient 1’s T-PLL cells proved to be intact. These results indicate that the CD20 molecules of the 3 patients’ leukemia/lymphoma cells have defects in the cytoplasmic C-terminal region which may impair the cytotoxic effect of rituximab such as CDC and ADCC and the defect may be due to post translational changes such as phosphorylation of serine and threonine residues. Table 1. Reactivity to different Abs specific to CD20 Pt Age Gender L27 (FACS) Rituximab (FACS) L26 (IHC) C-terminal Ab (WB) N-terminal Ab (WB) FACS, flow cytometry; IHC, immunohistochemistry; WB, Western blotting; +, positive; −, negative; ND, not determined 1 68 M + + − − + 2 75 M + + − − + 3 67 M + ND − − +
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Abbott, Daniel, Steven Kroft, Maria Hintzke, Luis Carrillo-Polanco, Ashley Cunningham, John Astle, Vasiliki Leventaki, and Alexandra Harrington. "Immunophenotypic Analysis of Peripheral T-Cell Lymphomas: A Single-Center Retrospective Review of Flow Cytometric Analysis." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S109. http://dx.doi.org/10.1093/ajcp/aqz121.012.
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Abstract Background Peripheral T-cell lymphomas (PTCLs) are heterogenous, mature T-cell neoplasms that are a diagnostic challenge, requiring a combination of morphologic assessment and ancillary studies. Flow cytometry (FC) is a tool used routinely in lymphoma diagnosis; however, most analyses are limited to B-cell evaluation and pathologists generally lack experience evaluating for PTCL. We aimed to describe the immunophenotypic aberrancies observed by FC in PTCL. Design PTCLs with FC were collected, excluding primary leukemic processes. Four- and eight-color FC data were reanalyzed with the following antigens (when available): CD2, CD3, CD4, CD5, CD7, CD8, CD30, CD45, CD45RO, CD56, and CD57. Lymphoma cells were compared to normal T cells and an isotype control. Antigen expression was defined as >20%. Results Thirty-eight cases were analyzed (29 males, 9 females, 6-86 years, median 62 years), including 29 PTCLs NOS, 4 angioimmunoblastic T-cell lymphomas (AITLs), 3 anaplastic large cell lymphomas, 1 δγ-TCL, and 1 hepatosplenic TCL from 15 bone marrows, 14 lymph nodes, 6 bloods, 2 fluids, and 1 skin. Twenty cases were CD4+, 4 were CD8+, 3 were dual +, and 10 were dual –. Thirty-seven cases (97%) showed global aberrant antigen patterns, median 4 aberrancies/case (1-8). Lymphoma cells accounted for 0.07% to 68% (median 2.6%) of total events. Aberrant CD7 expression was present in 34 of 38 (89%) and was underexpressed in 22 of 34 (65%). CD3 and CD5 were aberrant in 79% of cases each, with two-thirds showing underexpression. CD2 and CD45RO were aberrant in two-thirds of PTCLs, with overexpression in 61% and 92% of those cases, respectively. One AITL showed no aberrancies. Conclusions Nearly all PTCLs show immunophenotypic aberrancy compared to normal T cells. Most commonly, PTCL showed aberrant underexpression of CD7, CD3, and CD5 and overexpression of CD2 and CD45RO. Our data support FC panels with CD2, CD3, CD4, CD5, CD7, CD8, and CD45RO to optimize recovery of aberrant T cells.
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Tjønnfjord, G. E., O. P. Veiby, R. Steen, and T. Egeland. "T lymphocyte differentiation in vitro from adult human prethymic CD34+ bone marrow cells." Journal of Experimental Medicine 177, no. 6 (June 1, 1993): 1531–39. http://dx.doi.org/10.1084/jem.177.6.1531.
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Pluripotent lymphohematopoietic stem cells are probably confined to bone marrow cells expressing CD34 surface molecules. To investigate the capacity of adult human CD34+ bone marrow cells to differentiate along the T lymphoid lineage, we plated purified CD34+ cells from healthy adults in liquid culture on adherent thymic stromal cells prepared from HLA- or blood group-mismatched postnatal thymic tissue. We show that purified CD34+CD3-CD4-CD8- bone marrow cells contained progenitors with the ability to differentiate into CD4+ and CD8+ T lymphocytes expressing surface (s)CD3 and T cell receptor alpha/beta in vitro. These progenitors were found in the CD34+CD2+sCD3-CD4-CD8-, CD34+CD7+sCD3-CD4-CD8-, and CD34+CD2+CD7+sCD3-CD4-CD8-, as well as in the CD34+CD2-sCD3-CD4-CD8-, CD34+CD7-sCD3-CD4-CD8-, and CD34+CD2-CD7-sCD3-CD4-CD8- subsets, indicating that T lymphocyte progenitors sensitive to signals mediated by thymic stroma in vitro are not restricted to CD34+ cells already coexpressing early T lymphocyte-associated markers. Finally, we show that T lymphopoiesis was enhanced by c-kit ligand.
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Lukens, Michaël V., Debby Kruijsen, Frank E. J. Coenjaerts, Jan L. L. Kimpen, and Grada M. van Bleek. "Respiratory Syncytial Virus-Induced Activation and Migration of Respiratory Dendritic Cells and Subsequent Antigen Presentation in the Lung-Draining Lymph Node." Journal of Virology 83, no. 14 (May 6, 2009): 7235–43. http://dx.doi.org/10.1128/jvi.00452-09.
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ABSTRACT In the respiratory tract, different dendritic cell (DC) populations guard a tight balance between tolerance and immunity to infectious or harmless materials to which the airways are continuously exposed. For infectious and noninfectious antigens administered via different routes, different subsets of DC might contribute during the induction of T-cell tolerance and immunity. We studied the impact of primary respiratory syncytial virus (RSV) infection on respiratory DC composition in C57BL/6 mice. We also tracked the migration of respiratory DC to the lymph nodes and studied antigen presentation by lung-derived and lymph node-resident DC to CD4+ and CD8+ T cells. We observed a massive influx of mainly CD103− CD11bhigh CD11c+ conventional DC (cDC) and plasmacytoid DC during the first 7 days of RSV infection, while CD103+ CD11blow CD11c+ cDC disappeared from the lung. The two major subsets of lung tissue DC, CD103+ CD11blow CD11c+ and CD103− CD11bhigh CD11c+ cDC, both transported RSV RNA to the lung-draining lymph node. Furthermore, these lung-derived cDC subsets as well as resident LN DC, which did not contain viral RNA, displayed viral antigen by major histocompatibility complex class I and class II to CD8+ and CD4+ T cells. Taken together, our data indicate that during RSV infections, at least three DC subsets might be involved during the activation of lymph node-homing naïve and memory CD4+ and CD8+ T cells.
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Teoh, Jeffrey, Michael Stadnisky, Timothy Bullock, and Michael Brown. "Licensed NK-mediated response to murine cytomegalovirus specifically upregulates dendritic cell co-stimulatory ligands required in T cell priming (VIR1P.963)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 74.5. http://dx.doi.org/10.4049/jimmunol.192.supp.74.5.
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Abstract Ly49G2+ (G2+) NK cells mediate murine (M)CMV resistance in mice with the self-MHC Dk ligand expressed. A prior study showed that G2+ NK-mediated MCMV resistance resulted in increased numbers of conventional dendritic cells (cDC) and virus-specific CD8 T cells after infection, independent of CD4 T cells. However, the molecular basis underlying licensed NK-mediated enhancement of T-cell immunity is unknown. Here we examined the role of co-stimulatory ligands expressed in splenic cDC after MCMV infection. An increase in the intracellular expression of both CD86 and CD70 was observed by 72-hr, first in the CD8α+ DC and then in the CD11b+ DC. To test functionality, we used CD86 and CD70 mAbs to block co-stimulation before infection. CD86-block had no effect on CD8 T cells. In contrast, CD70-block impaired both the frequency and the numbers of MCMV-specific CD8 T cells without perturbing cDC numbers, cDC maturation, or G2+ NK-mediated viral control. We next examined the importance of CD70-CD27 signaling in CD27-/- mice with the self-ligand Dk expressed. We observed similar deficits in Ag-specific CD8 T cells, despite having intact G2+ NK-mediated MCMV control. Moreover, CD8 T cells in both CD70-blocked and CD27-/- infected mice responded to MCMV peptide re-stimulation with less degranulation and cytokine production. We infer that a licensed G2+ NK-mediated response to MCMV upregulates co-stimulatory molecule expression in cDC that is needed to efficiently prime CD8 T cells.
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Delgado-Arévalo, C., M. Calvet-Mirabent, A. Triguero-Martinez, E. Vazquez de Luis, A. Benguría-Filippini, D. Calzada, I. Sánchez-Cerrillo, et al. "POS0367 NLRC4 AND FC-γ-R CROSSTALK ON CD1C+ DENDRITIC CELLS DIFFERENTIALLY CONTRIBUTES TO RHEUMATOID ARTHRITIS IMMUNOPATHOLOGY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 413.2–413. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3192.
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Background:Rheumatoid arthritis (RA) is an autoimmune disorder in which Th17 cells, B cells and inflammatory cytokines (1-3) contribute to joint tissue damage, however the role of specific myeloid populations to immunopathogenesis of RA remains unclear.Objectives:To address this question, we studied transcriptional, phenotypical and functional characteristics of monocytes (Mo), CD1c+ and CD141+ conventional dendritic cells (cDC) from RA patients.Methods:Frequencies and maturation patterns of Lin-CD14-HLADR+ plasmacytoid (CD11c-), CD1c+ and CD141+ cDC (CD11c+) subsets and CD14+ Mo from n=25 RA patients at baseline were analyzed by multicolor flow cytometry. In addition, longitudinal studies on the evolution of these populations after treatment initiation were conducted on a smaller group of RA patients. Moreover, CD1c+ and CD141+ cDC subsets and total Mo were sorted from the peripheral blood from n=4 untreated RA and healthy individuals and the synovial fluid from n=3 RA and chondrocalcinosis patients. Differential transcriptional patterns within each population were analyzed by RNAseq. Functional validation of targets were performed in vitro with cDC subsets isolated form the synoviual fluid of RA patients. Finally, silencing of expression of NLRC4 and NLRP3 on CD1c+cDCs was performed with specific siRNAs.Results:Both CD1c+ (p=0.0001) and CD141+ (p=0.0008) cDCs were significantly depleted from the blood and enriched in the synovial fluid from untreated RA patients, but proportions of CD1c+ cDCs were more significantly recovered after treatment initiation and associated with improved clinical parameters. In addition, specific increased expression levels of the IgG-Fc receptor CD64 on CD1c+ cDC was associated with higher DAS28 (p=0.0002). Moreover, differential transcriptional patterns of circulating CD1c+cDCs from RA patients were characterized by genes linked to toll-like receptor, Fc-receptor, inflammasome pathways and elevated CCR2 expression (p=0.016), while CD141+cDCs transcribed interferon-related genes. Importantly, CCR2+ CD64Hi CD1c+cDCs from the synovial fluid from RA patients transcribed proinflammatory cytokines such as IL1-β, CCL3 and IL-8, actively expressed the inflammasome mediator caspase 1 and were more effective activating pathogenic IFNγ+IL-17+ CD4+ T cells in vitro than CD141+ cDC (p=0.0019). These functional profiles could be artificially induced stimulating CD1c+ cDCs with dsDNA in the presence of IgGs and was dependent on caspase 1 and the NLRC4 inflammasome.Conclusion:Our data provides novel insights about specific activation and functional patterns on CD1c+cDC contributing to RA pathogenesis and identifies new sensors that could represent novel therapeutic target to treat RA.References:[1]Alvandpur N, Tabatabaei R, Tahamoli-Roudsari A, Basiri Z, Behzad M, Rezaeepoor M, et al. Circulating IFN-gamma producing CD4+ T cells and IL-17A producing CD4+ T cells, HLA-shared epitope and ACPA may characterize the clinical response to therapy in rheumatoid arthritis patients. Human immunology. 2020.[2]Nistala K, Adams S, Cambrook H, Ursu S, Olivito B, de Jager W, et al. Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proceedings of the National Academy of Sciences of the United States of America. 2010;107(33):14751-6.[3]Chapuy-Regaud S, Nogueira L, Clavel C, Sebbag M, Vincent C, Serre G. IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullinated fibrin. Clinical and experimental immunology. 2005;139(3):542-50.Disclosure of Interests:None declared
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Barcena, A., MO Muench, AH Galy, J. Cupp, MG Roncarolo, JH Phillips, and H. Spits. "Phenotypic and functional analysis of T-cell precursors in the human fetal liver and thymus: CD7 expression in the early stages of T- and myeloid-cell development." Blood 82, no. 11 (December 1, 1993): 3401–14. http://dx.doi.org/10.1182/blood.v82.11.3401.3401.
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Abstract It has been proposed that the CD7 molecule is the first antigen expressed on the membrane of cells committed to the T-cell lineage during human fetal T-cell ontogeny. To further identify the pre-T cell subpopulation that migrates to the thymus early in ontogeny, we analyzed the phenotypic and functional characteristics of the fetal liver populations separated on the basis of CD7 expression. Three populations expressing different levels of CD7 were observed: CD7bright, CD7dull, and CD7-. A CD7bright population depleted of mature T, B, and myeloid cells (lineage negative, lin-) and mostly composed of CD56+ CD34- natural killer cells did not mature into T cells in a fetal thymic organ culture (FTOC) assay and was devoid of myeloid progenitors in a clonal colony-forming cell assay. In contrast, the CD7-/dull CD34+ lin- populations were capable of differentiating into phenotypically mature T cells after injection into FTOC and contained early myeloid progenitors. Here we phenotypically compared the fetal liver CD7 populations with the most immature fetal thymic subset that differentiated in the FTOC assay, namely the triple negative (TN, CD3- CD4-CD8-) thymocytes. Fetal TN lin- expressed high levels of CD34 marker and were further subdivided by their expression of CD1 antigen, because CD1- TN thymocytes express higher levels of CD34 antigen compared with CD1+ TN cells. CD1- lin -TN thymocytes are characterized by expressing high levels of CD2, CD7, and CD34 markers and dull levels of CD5, CD10, and CD28 molecules. We could not find fetal liver pre-T cells with a phenotype equivalent to that of TN thymocytes. Our data show that CD7 does not necessarily identify T-cell precursors during fetal T-cell development and strongly support the hypothesis that the acquisition of early T-cell markers as CD2, CD28, and CD5 molecules on the cell surface of T-cell progenitors takes place intrathymically.
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Barcena, A., MO Muench, AH Galy, J. Cupp, MG Roncarolo, JH Phillips, and H. Spits. "Phenotypic and functional analysis of T-cell precursors in the human fetal liver and thymus: CD7 expression in the early stages of T- and myeloid-cell development." Blood 82, no. 11 (December 1, 1993): 3401–14. http://dx.doi.org/10.1182/blood.v82.11.3401.bloodjournal82113401.
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It has been proposed that the CD7 molecule is the first antigen expressed on the membrane of cells committed to the T-cell lineage during human fetal T-cell ontogeny. To further identify the pre-T cell subpopulation that migrates to the thymus early in ontogeny, we analyzed the phenotypic and functional characteristics of the fetal liver populations separated on the basis of CD7 expression. Three populations expressing different levels of CD7 were observed: CD7bright, CD7dull, and CD7-. A CD7bright population depleted of mature T, B, and myeloid cells (lineage negative, lin-) and mostly composed of CD56+ CD34- natural killer cells did not mature into T cells in a fetal thymic organ culture (FTOC) assay and was devoid of myeloid progenitors in a clonal colony-forming cell assay. In contrast, the CD7-/dull CD34+ lin- populations were capable of differentiating into phenotypically mature T cells after injection into FTOC and contained early myeloid progenitors. Here we phenotypically compared the fetal liver CD7 populations with the most immature fetal thymic subset that differentiated in the FTOC assay, namely the triple negative (TN, CD3- CD4-CD8-) thymocytes. Fetal TN lin- expressed high levels of CD34 marker and were further subdivided by their expression of CD1 antigen, because CD1- TN thymocytes express higher levels of CD34 antigen compared with CD1+ TN cells. CD1- lin -TN thymocytes are characterized by expressing high levels of CD2, CD7, and CD34 markers and dull levels of CD5, CD10, and CD28 molecules. We could not find fetal liver pre-T cells with a phenotype equivalent to that of TN thymocytes. Our data show that CD7 does not necessarily identify T-cell precursors during fetal T-cell development and strongly support the hypothesis that the acquisition of early T-cell markers as CD2, CD28, and CD5 molecules on the cell surface of T-cell progenitors takes place intrathymically.
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Weimer, R., V. Daniel, R. Zimmermann, K. Schimpf, and G. Opelz. "Autoantibodies against CD4 cells are associated with CD4 helper defects in human immunodeficiency virus-infected patients." Blood 77, no. 1 (January 1, 1991): 133–40. http://dx.doi.org/10.1182/blood.v77.1.133.133.
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Abstract To investigate whether autoantibodies against CD4-positive lymphocytes might induce helper dysfunction, autoantibody formation and T-cell function was examined simultaneously in 61 hemophilia patients. Twenty patients were human immunodeficiency virus (HIV)-negative, 26 HIV- positive stage CDC II or III, and 15 were HIV-positive stage CDC IV. T lymphocytes, CD4-positive, or CD8-positive T subsets were cocultured with B lymphocytes and pokeweed mitogen (PWM) for 6 days and Ig- secreting cells were assessed in a reverse hemolytic plaque assay. The presence of IgM, IgG, C3d, or gp120 on the surface of T cells or T subsets was analyzed by flow cytometry. Autoantibodies against CD4- positive T cells were not detected in controls or HIV-negative patients, but were common in HIV-positive patients (20 of 41 patients). In patients with autoantibodies we found an increased incidence of CD4 helper defects (P less than .0001 in CDC II or III patients; P less than .02 in CDC IV patients). 12 of 13 patients with IgM autoantibodies and 4 of 4 with IgG autoantibodies showed CD4 helper defects. Complement fixation had no relevance. Autoantibody formation against CD4 cells was not due to increased in vivo B-cell stimulation (spontaneous plaque formation: 611 +/- 204 PFC/10(6) B cells in autoantibody-negative patients v 650 +/- 202 PFC/10(6) B cells in autoantibody-positive patients; not significant). Thus, our results suggest that autoantibody formation is not caused by a general state of in vivo B-cell activation. Rather, the production of autoantibodies appears to coincide with defects in B-cell proliferation or differentiation, as shown by reduced mitogen-stimulated B-cell responses in CDC II and III patients (P less than .05). Autoantibodies against CD4 cells appear to be involved in the pathogenesis of CD4 helper defects of HIV-infected patients.
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Weimer, R., V. Daniel, R. Zimmermann, K. Schimpf, and G. Opelz. "Autoantibodies against CD4 cells are associated with CD4 helper defects in human immunodeficiency virus-infected patients." Blood 77, no. 1 (January 1, 1991): 133–40. http://dx.doi.org/10.1182/blood.v77.1.133.bloodjournal771133.
Full textAbstract:
To investigate whether autoantibodies against CD4-positive lymphocytes might induce helper dysfunction, autoantibody formation and T-cell function was examined simultaneously in 61 hemophilia patients. Twenty patients were human immunodeficiency virus (HIV)-negative, 26 HIV- positive stage CDC II or III, and 15 were HIV-positive stage CDC IV. T lymphocytes, CD4-positive, or CD8-positive T subsets were cocultured with B lymphocytes and pokeweed mitogen (PWM) for 6 days and Ig- secreting cells were assessed in a reverse hemolytic plaque assay. The presence of IgM, IgG, C3d, or gp120 on the surface of T cells or T subsets was analyzed by flow cytometry. Autoantibodies against CD4- positive T cells were not detected in controls or HIV-negative patients, but were common in HIV-positive patients (20 of 41 patients). In patients with autoantibodies we found an increased incidence of CD4 helper defects (P less than .0001 in CDC II or III patients; P less than .02 in CDC IV patients). 12 of 13 patients with IgM autoantibodies and 4 of 4 with IgG autoantibodies showed CD4 helper defects. Complement fixation had no relevance. Autoantibody formation against CD4 cells was not due to increased in vivo B-cell stimulation (spontaneous plaque formation: 611 +/- 204 PFC/10(6) B cells in autoantibody-negative patients v 650 +/- 202 PFC/10(6) B cells in autoantibody-positive patients; not significant). Thus, our results suggest that autoantibody formation is not caused by a general state of in vivo B-cell activation. Rather, the production of autoantibodies appears to coincide with defects in B-cell proliferation or differentiation, as shown by reduced mitogen-stimulated B-cell responses in CDC II and III patients (P less than .05). Autoantibodies against CD4 cells appear to be involved in the pathogenesis of CD4 helper defects of HIV-infected patients.
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Oshi, Masanori, Stephanie Newman, Yoshihisa Tokumaru, Li Yan, Ryusei Matsuyama, Pawel Kalinski, Itaru Endo, and Kazuaki Takabe. "Plasmacytoid Dendritic Cell (pDC) Infiltration Correlate with Tumor Infiltrating Lymphocytes, Cancer Immunity, and Better Survival in Triple Negative Breast Cancer (TNBC) More Strongly than Conventional Dendritic Cell (cDC)." Cancers 12, no. 11 (November 12, 2020): 3342. http://dx.doi.org/10.3390/cancers12113342.
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Dendritic cells (DC) represent a major antigen-presenting cell type in the tumor immune microenvironment (TIME) and play an essential role in cancer immunity. Conventional DC (cDC) and plasmacytoid DC (pDC) were defined by the xCell algorithm and a total of 2968 breast cancer patients (TCGA and METABRIC) were analyzed. We found that triple-negative breast cancer (TNBC) had a high fraction of cDC and pDC compared to the other subtypes. In contrast to cDC, high pDC in TNBC was significantly associated with better disease-specific and disease-free survival consistently in both cohorts. High cDC TNBC tumors enriched not only inflammation and immune-related, but also metastasis-related gene sets in Gene Set Enrichment Analysis, whereas high pDC TNBC enriched inflammation and immune -related gene sets including IFN-γ signaling more strongly than cDC. pDC TNBC correlated with CD8+, CD4+ memory, IFN-γ score, and cytolytic activity stronger than cDC TNBC. High pDC TNBC were associated with a high fraction of anti-cancer immune cells and high expression of all the immune check point molecules examined. In conclusion, pDC levels correlated with the infiltration of immune cells and patient survival in TNBC more strongly than cDC; this is the first study suggesting the clinical relevance of pDC infiltration in TNBC.
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Ferris, Stephen T., Renee Wu, Vivek Durai, Theresa L. Murphy, and Kenneth M. Murphy. "cDC1 prime and receive help from CD4 T cells to promote anti-tumor responses." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 164.21. http://dx.doi.org/10.4049/jimmunol.204.supp.164.21.
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Abstract CD4 T cells are thought to help promote anti-tumour responses by ‘licensing’ antigen presenting cells (APCs) that activate CD8 T cells. Conventional type 1 dendritic cells (cDC1s) are responsible for cross-presentation of tumour-derived antigens to CD8 T cells. Prevailing models presume that the cDC1 is licensed by CD4 T cells that are themselves activated by a distinct cDC subset, the cDC2. The recent finding that neoantigens presented by major histocompatibility complex (MHC) class II molecules can promote rejection of tumours that lack MHC class II (MHC-II) surface expression is consistent with an indirect action of CD4 T cells, such as cDC1 licensing. However, no study has directly identified the APC that primes the CD4 T cells responsible for licensing or clearly identified the target of CD4 licensing in vivo. Here, we generated cDC1-specific Cre expressing mouse strain to inactivate or induce expression of MHC-I, MHC-II, or CD40 specifically within the cDC1 lineage. Using a tumour model that relies on CD8 T cells and CD4 T cells for rejection, we discovered that priming of CD4 T cells against tumour-derived antigens, in contrast to soluble antigens, relied overwhelmingly on the cDC1 and not the cDC2. cDC1 do not simply transport antigen to lymph nodes for processing by cDC2, since lack of MHC-II expression on cDC1 prevented CD4 T cell priming. We also found that CD40 signaling not only affects licensing of cDC1 for CD8 T cell priming, but is also critical for the activation of CD4 T cells. Thus, in the setting of tumour-derived antigens, cDC1 function as an autonomous platform capable of priming both CD4 and CD8 T cells and orchestrating their cross-talk required for optimal anti-tumour immunity.
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Szulc-Dąbrowska, Lidia, Zuzanna Biernacka, Michał Koper, Justyna Struzik, Małgorzata Gieryńska, Ada Schollenberger, Iwona Lasocka, and Felix N. Toka. "Differential Activation of Splenic cDC1 and cDC2 Cell Subsets following Poxvirus Infection of BALB/c and C57BL/6 Mice." Cells 13, no. 1 (December 20, 2023): 13. http://dx.doi.org/10.3390/cells13010013.
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Conventional dendritic cells (cDCs) are innate immune cells that play a pivotal role in inducing antiviral adaptive immune responses due to their extraordinary ability to prime and polarize naïve T cells into different effector T helper (Th) subsets. The two major subpopulations of cDCs, cDC1 (CD8α+ in mice and CD141+ in human) and cDC2 (CD11b+ in mice and CD1c+ in human), can preferentially polarize T cells toward a Th1 and Th2 phenotype, respectively. During infection with ectromelia virus (ECTV), an orthopoxvirus from the Poxviridae family, the timing and activation of an appropriate Th immune response contributes to the resistance (Th1) or susceptibility (Th2) of inbred mouse strains to the lethal form of mousepox. Due to the high plasticity and diverse properties of cDC subpopulations in regulating the quality of a specific immune response, in the present study we compared the ability of splenic cDC1 and cDC2 originating from different ECTV-infected mouse strains to mature, activate, and polarize the Th immune response during mousepox. Our results demonstrated that during early stages of mousepox, both cDC subsets from resistant C57BL/6 and susceptible BALB/c mice were activated upon in vivo ECTV infection. These cells exhibited elevated levels of surface MHC class I and II, and co-stimulatory molecules and showed enhanced potential to produce cytokines. However, both cDC subsets from BALB/c mice displayed a higher maturation status than that of their counterparts from C57BL/6 mice. Despite their higher activation status, cDC1 and cDC2 from susceptible mice produced low amounts of Th1-polarizing cytokines, including IL-12 and IFN-γ, and the ability of these cells to stimulate the proliferation and Th1 polarization of allogeneic CD4+ T cells was severely compromised. In contrast, both cDC subsets from resistant mice produced significant amounts of Th1-polarizing cytokines and demonstrated greater capability in differentiating allogeneic T cells into Th1 cells compared to cDCs from BALB/c mice. Collectively, our results indicate that in the early stages of mousepox, splenic cDC subpopulations from the resistant mouse strain can better elicit a Th1 cell-mediated response than the susceptible strain can, probably contributing to the induction of the protective immune responses necessary for the control of virus dissemination and for survival from ECTV challenge.
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Greenberg, JM, and JH Kersey. "Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia." Blood 69, no. 1 (January 1, 1987): 356–60. http://dx.doi.org/10.1182/blood.v69.1.356.356.
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Abstract The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is thought to contribute to the diversity of certain immunoglobulin and T cell receptor gene rearrangements through the addition of random nucleotides at their variable (V)-joining (J) region junctions. An acute lymphoblastic leukemia (ALL) with an immature T cell phenotype (CD7+, CD5+, CD1+/-, CD2+/-, CD3-, CD4-, CD8-) was found to be TdT+ with germline immunoglobulin heavy chain, T cell receptor beta chain, and T cell gamma chain genes. The data indicate that TdT expression can precede T gamma and T beta rearrangement during T lymphoid ontogeny consistent with its proposed association with the T cell receptor rearrangement process. Southern analysis of certain cases of T-ALL may not result in the detection of a monoclonal population of cells.
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Greenberg, JM, and JH Kersey. "Terminal deoxynucleotidyl transferase expression can precede T cell receptor beta chain and gamma chain rearrangement in T cell acute lymphoblastic leukemia." Blood 69, no. 1 (January 1, 1987): 356–60. http://dx.doi.org/10.1182/blood.v69.1.356.bloodjournal691356.
Full textAbstract:
The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) is thought to contribute to the diversity of certain immunoglobulin and T cell receptor gene rearrangements through the addition of random nucleotides at their variable (V)-joining (J) region junctions. An acute lymphoblastic leukemia (ALL) with an immature T cell phenotype (CD7+, CD5+, CD1+/-, CD2+/-, CD3-, CD4-, CD8-) was found to be TdT+ with germline immunoglobulin heavy chain, T cell receptor beta chain, and T cell gamma chain genes. The data indicate that TdT expression can precede T gamma and T beta rearrangement during T lymphoid ontogeny consistent with its proposed association with the T cell receptor rearrangement process. Southern analysis of certain cases of T-ALL may not result in the detection of a monoclonal population of cells.
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Candon, Sophie, Blandine Rammaert, Anne Perrine Foray, Baptiste Moreira, Maria Pilar Gallego Hernanz, Lucienne Chatenoud, and Olivier Lortholary. "Chronic Disseminated Candidiasis During Hematological Malignancies: An Immune Reconstitution Inflammatory Syndrome With Expansion of Pathogen-Specific T Helper Type 1 Cells." Journal of Infectious Diseases 221, no. 11 (December 27, 2019): 1907–16. http://dx.doi.org/10.1093/infdis/jiz688.
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Abstract Background Chronic disseminated candidiasis (CDC) is a rare disease that mostly occurs after chemotherapy-induced prolonged neutropenia in patients with hematological malignancies. It is believed to ensue from Candida colonization, breach of the intestinal epithelial barrier, and venous translocation to organs. Fungal blood or liver biopsy cultures are generally negative, suggesting the absence of an ongoing invasive fungal disease. Methods To unravel the contribution of the immune system to CDC pathogenesis, we undertook a prospective multicentric exploratory study in 44 CDC patients at diagnosis and 44 matched controls. Results Analysis of Candida-specific T-cell responses using enzyme-linked immunospot assays revealed higher numbers of interferon (IFN)γ-producing T cells reactive to mp65 or candidin in 27 CDC cases compared with 33 controls. Increased plasma levels of soluble CD25, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and IL-10 and lower levels of IL-2 were observed in CDC patients versus controls. Neutrophilia and higher levels of CD4 and CD8 T-cell activation were found in CDC patients as well as increased proportions of CXCR3-expressing TCRγδ +Vδ2+ cells. Conclusions The expansion of Candida-specific IFNγ-producing T cells together with features of T-cell activation and systemic inflammation identified here support the view that CDC belongs to the broad spectrum of fungal-associated immune reconstitution inflammatory syndromes.
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Terstappen, LW, S. Huang, and LJ Picker. "Flow cytometric assessment of human T-cell differentiation in thymus and bone marrow." Blood 79, no. 3 (February 1, 1992): 666–77. http://dx.doi.org/10.1182/blood.v79.3.666.bloodjournal793666.
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Using multidimensional flow cytometry we have defined and quantified the human T-cell differentiation pathway, focusing on those events occurring among the most immature thymocytes and putative bone marrow (BM) T-precursors. Early thymocytes were found to express the CD34 antigen and consisted of a mean 1.2% of cells within human pediatric (n = 9) and 2.0% in fetal thymi (n = 4). All CD34+ thymocytes were atypical blast by morphology, expressed intracytoplasmatic, but not cell surface, CD3, and were cell surface CD2+, CD5+, CD7+, CD38+, CD45+, CD45RA+, CD49d+, and LECAM-1(Leu8)high. CD34high thymocytes lacked surface expression of CD4 and CD8, but as CD34 expression diminished there was a coordinate increase in CD4 levels, followed by the appearance of CD8. The expression of CD1 and CD10 also increased concomitant with the loss of CD34, whereas expression of LECAM-1 diminished with CD34 downregulation. The differential expression of these antigens on early thymocytes (as well as the number of thymocytes displaying these patterns) was highly reproducible among the nine pediatric and four fetal specimens examined, suggesting a precise, stereotyped regulation of early differentiation events. Cell populations with antigen expression patterns suggestive of pluripotent stem cell (CD34high, CD38-), or non-T-lineage committed stem cells (CD34+, CD33+ or CD34+, CD19+) were not identified in either fetal or pediatric thymi (sensitivity = 1/10(4)). The presence of cells with the antigenic profile of the earliest CD34+ thymocytes was explored in human BM. Putative BM T-cell precursors with the appropriate phenotype (CD34+, CD7+, CD5+, CD2+, LECAM-1high) were readily identified in fetal specimens (constituting +/- 2% of the CD34+ population), but could not be reliably detected in adults. In contrast with thymi, only 13% of these cells expressed cytoplasmatic CD3, suggesting the presence of the immediate precursor of the putative prothymocyte population. This was further supported by the detection of CD34bright, CD7+, CD2-, CD5-, LECAM-1moderate cells in fetal specimens. Our results document the flow of cell surface differentiation during T-lymphopoiesis and suggest that T-lineage features are first acquired in the BM. The ability to reproducibly identify and isolate T-cell precursor populations of precisely defined maturational stage in marrow and thymus by multiparameter flow cytometry will facilitate characterization of the molecular events controlling T-lineage differentiation.
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Meng, Chuang, Jun Liu, Xilong Kang, Zhengzhong Xu, Shuangyuan Xu, Xin Li, Zhiming Pan, Xiang Chen, and Xinan Jiao. "Discrepancy in Response of Mouse Dendritic Cells against BCG: Weak Immune Effects of Plasmacytoid Dendritic Cells Compared to Classical Dendritic Cells despite the Uptake of Bacilli." Tropical Medicine and Infectious Disease 8, no. 3 (February 25, 2023): 140. http://dx.doi.org/10.3390/tropicalmed8030140.
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Tuberculosis (TB), a zoonosis characterized by chronic respiratory infections, is mainly caused by Mycobacterium tuberculosis and is associated with one of the heaviest disease burdens in the world. Dendritic cells (DCs) play a key role and act as a bridge between innate and adaptive immune responses against TB. DCs are divided into distinct subsets. Currently, the response of DCs to mycobacterial infections is poorly understood. Herein, we aimed to evaluate the responses of splenic conventional DCs (cDC) and plasmacytoid DCs (pDC), subsets to Bacillus Calmette–Guérin (BCG) infection in mice. Splenic pDC had a significantly higher infection rate and intracellular bacterial count than cDC and the CD8+ and CD8− cDC subsets after BCG infection. However, the expression levels of CD40, CD80, CD86, and MHC-II molecules were significantly upregulated in splenic cDC and the CD8 cDC subsets compared to pDC during BCG infection. Splenic cDC had a higher expression of IFN-γ and IL-12p70 than pDC, whereas pDC had higher levels of TNF-α and MCP-1 than cDC in mice infected with BCG. At early stages of immunization with BCG containing the Ag85A protein, splenic cDC and pDC could present the Ag85A peptide to a specific T hybridoma; however, cDC had a stronger antigen presenting activity than pDC. In summary, splenic cDC and pDC extensively participate in mouse immune responses against BCG infection in vivo. Although pDC had a higher BCG uptake, cDC induced stronger immunological effects, including activation and maturation, cytokine production, and antigen presentation.
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Balasubramaniam, Thara, Clive Carter, Marie von Lilienfeld-Toal, Paul Evans, Maria Helena Gilleece, and Gordon Cook. "Delayed Donor B-Cell Reconstitution After Allogeneic Stem Cell Transplantation Is Associated with Increased Risk of Relapse but Protects From Chronic Graft Versus Host Disease." Blood 114, no. 22 (November 20, 2009): 2228. http://dx.doi.org/10.1182/blood.v114.22.2228.2228.
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Abstract Abstract 2228 Poster Board II-205 B lymphocyte homeostasis may have a role in regulating the immune response, both stimulatory & regulatory/tolerogenic, in Allogeneic Stem Cell Transplantation (AlloSCT). The predictive relationship of donor B-cell reconstitution with relapse risk, chronic Graft versus Host Disease (cGvHD) & overall survival (OS) was investigated. We performed prospective comprehensive immune reconstitution studies in 71 patients undergoing AlloSCT (Matched Related Donor=33, Matched Unrelated Donor =34, Umbilical Cord Blood =3, Haplo-identical Related Donor =1) for haematological malignancy & marrow failure syndromes who were available for follow-up beyond Day+100. 27 patients received full intensity conditioning & 44 reduced intensity conditioning with 34 patients receiving Alemtuzumab & 8 patients receiving ATG as in vivo T-cell depletion with a median PAM score of 22 (range 8-36). The grafts were bone marrow in 23, peripheral blood stem cells in 40 and umbilical cord blood in 3 with a median CD34+cell dose of 4.3×106/kg (range 0.8-10.5) & median duration of immune-suppression of 7.1 months (range 2, 49). Samples were analysed for lymphocyte subsets by multi-parameter flow cytometry & cell subset-specific Complete Donor Chimerism (CDC) by single tandem repeat PCR at day (D)+100, D+180, D+270 and D+365. The proportion of patients with a CD4+, CD8+, CD19+ & NK cell count within the normal range at D+100 & D+180 were: 10% & 27% for CD4+, 28% & 57% for CD8+, 24% & 57% for B-cells, 68% & 83% for NK cells, respectively. The proportion of patients with a CD4+, CD8+, CD19+ & NK cell CDC at D+100 & D+180 were: 80% & 78% for CD4+, 86% & 80% for CD8+, 89% & 91% for B-cells, respectively. 28 patients (38%) experienced cGvHD (22/28 extensive) with a median time to onset of 4 months (range 3-12) & median duration of immune suppression of 14.5 months (range 6.9-48.3). In univariate analysis, only the B-cell CDC at D+100 was associated with a higher incidence of cGvHD (mean 99.8%±0.2% vs. 90.4%±4.4 CDC, respectively; p=0.044) though a trend was seen in regard to D+180 B-cell CDC. No influence of mature/immature B-cell reconstitution at D+100 or D+180 was detected. 24 patients (34%) have relapsed at a median of 5.8 months (range 3-34). A trend to lower absolute B-cell counts at D+100 & D+180 was seen in those who relapsed with significantly lower B-cell CDC at D+100 and D+180 in those who relapsed compared to those who did not (D+100: mean 87.9%±2.4% vs. 98.3%±1.5 CDC, respectively; p=0.038; D+180: mean 80±5.6 vs. 100%±0 CDC, respectively; p=0.013). With a median follow-up of 16.7 months (range 5.1-51.8), 27 (38%) have died (disease progression n=12, infection n=4, GvHD-related n=6). In univariate analysis, no effect on OS was demonstrated by the absolute B-cell count or B-cell CDC at D+100 or D+180, though a trend was seen to lower levels in those who did not survive. In conclusion, delayed donor B-cell reconstitution was associated with a higher relapse risk. On the other hand, cGvHD was associated with higher early donor B-cell reconstitution, which suggests that residual recipient B-cells after AlloSCT may protect from cGvHD. This data provides further clinical evidence for a role of B-cells in the immune-modulation associated with the graft-versus-tumour/graft-versus-host disease paradigm of AlloSCT. Disclosures: No relevant conflicts of interest to declare.
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Maroof, Asher, and Paul M. Kaye. "Temporal Regulation of Interleukin-12p70 (IL-12p70) and IL-12-Related Cytokines in Splenic Dendritic Cell Subsets during Leishmania donovani Infection." Infection and Immunity 76, no. 1 (November 12, 2007): 239–49. http://dx.doi.org/10.1128/iai.00643-07.
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ABSTRACT Dendritic cells (DC) play an essential role in initiating and directing T-cell responses, in part by production of interleukin-12p70 (IL-12p70), IL-23, and IL-27. However, comparative studies on the capacity for cytokine production of DC subsets are rare. Here, we compare splenic CD8α+, CD4+, and double-negative (DN) DC, isolated 5 h to 28 days after Leishmania donovani infection, for (i) production of IL-12p70, (ii) accumulation of IL-12/23p40, IL-12p35, IL-23p19, and IL-27p28 mRNAs, and (iii) their capacity to direct CD4+ T-cell differentiation. At 5 h, conventional DC (cDC) accumulated mRNA for IL-12/23p40 (CD8α>CD4>DN), IL-23p19 (CD4>CD8α>DN), and IL-27p28 (CD8α>CD4>DN), in an infection dose-dependent manner. IL-12p70 was restricted to CD8α+ cDC, reflecting the subset-specific accumulation of IL-12p35 mRNA. In contrast, cDC from mice infected for 14 to 28 days accumulated little mRNA for IL-12p40 and IL-12p19, though IL-27p28 mRNA remained detectable (CD8α>DN>CD4). IL-12p70 secretion by CD8α+ cDC was also absent, reflecting deficient IL-12/23p40, rather than IL-12p35, mRNA accumulation. The capacity of CD8α+ cDC isolated early after infection to direct Th1 cell differentiation was mediated through IL-12/23p40, whereas this ability in CD4+ and DN cDC was independent of IL-12/23p40 and did not result from overexpression of Delta 4 Notch-like ligand. However, DN cDC produced gamma interferon (IFN-γ) and also contained a rare population of CD11chi DX5+ IFN-γ-producing cells. Our data illustrate the extensive diversity in, and temporal regulation of, splenic cDC subsets during infection and suggest caution in interpreting data obtained with unfractionated or minimally purified DC.
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Nicolau, José Eduardo, Gil Benard, Luis Augusto Marcondes Fonseca, Jorge Simão Rosário Casseb, Maria Natomi Sato, Marcia Cianga, Mauri Massani Tanji, Therezinha Ferreira Lorenzi, and Alberto José da Silva Duarte. "HIV heterosexual transmission to stable sexual partners of HIV-infected Brazilian hemophiliacs." Sao Paulo Medical Journal 114, no. 3 (June 1996): 1186–89. http://dx.doi.org/10.1590/s1516-31801996000300008.
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Nineteen Brazilian HIV-infected hemophiliacs and their stable heterosexual sexual partners were studied with the aim of assessing the rate of HIV transmission in this at risk group. The mean length of relationship between couples was 7.4 years. The hemophiliac men were Class II (n=6), III (n=11) and IVa (n=2) of the CDC classification. They had decreased CD4+ and elevated CD8+ cell numbers; five had p24 antigenemia. We found 3 HIV-infected women (15.8 percent) by routine and confirmatory tests, a prevalence similar to that seen in other countries. They were asymptomatic and had no detectable p24 antigenemia. The 3 seropositive women's partners were Class II and III-CDC, and had normal CD4+ and CD8+ values and no p24 antigenemia. All seronegative women also had normal CD4+ and CD8+ numbers, except for elevated CD8+ cells in three of them, but immune abnormalities had already been seen in some seronegative partners at high risk for HIV infection. Our results reinforce previous suggestions that heterosexual transmission to stable female partners occurs preferentially early after initiation of sexual exposure, and possibly when the transmitter has high levels of viremia and regular sexual activity.
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Zheng, Hong, Scott Antonia, Mark J. Cantwell, Xiaoqing Yu, and Amer A. Beg. "Abstract 3542: Oncolytic adenovirus encoding transgenes for IFN-beta and recombinant CD40 ligand promotes conventional dendritic cell activation and trafficking with enhanced tumor infiltrating lymphocytes for effective cancer immunotherapy." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3542. http://dx.doi.org/10.1158/1538-7445.am2022-3542.
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Abstract Clinical studies have shown that pre-existing tumor-reactive T cells are critically important for effective cancer immunotherapy. Methods to augment the number and functionality of tumor-reactive T cells are therefore vital. Given that cytotoxic CD8 T cell priming requires conventional dendritic cells (cDC), we hypothesized that strategies to enhance cDC functionality in tumors would augment anti-tumor CD8 T cell responses. CD40 and type 1 IFN signaling pathways each promote the cross-presentation function of cDCs to activate CD8 T cells. However, it is unclear whether these pathways are functionally independent and whether their combined activation in tumor cDC leads to higher levels of T cell priming. Using adenovirus vectors, we tested the impact of expression of IFNβ and a chimeric membrane-stable CD40 ligand (MEM40) in syngeneic mouse tumor models. Compared to intratumoral administration of each individual transgene-encoding adenovirus, combined MEM40 + IFNβ expression resulted in the best tumor growth control, highest levels of tumor infiltrating lymphocytes (TILs), and systemic CD8 T cell responses. MEM40 and IFNβ were independently capable of enhancing T cell responses as we found IFNβ in CD40-/- mice and MEM40 in type 1 IFN receptor IFNAR1-/- mice induced a strong T cell response. These results were consistent with a cDC-mediated priming mechanism. Studies with cDC1 deficient BATF3-/- mice revealed a crucial role of this cDC subset in MEM40 + IFNβ induced T cell responses. IFNβ alone and MEM40 + IFNβ triggered increase in lymph node (LN) homing receptor CCR7 expression in cDC1 concurrent with a reduction in cDC1 in tumors and gain in tumor draining LNs. Simultaneously, combined MEM40 + IFNβ combination led to the highest levels of expression of CD80 and CD86 co-stimulatory molecules in both tumor and LN cDC1. Single cell (sc)-RNA sequencing of tumor DCs further showed that MEM40 + IFNβ led to the highest proportion of a recently defined mature/regulatory cDC subset characterized by high expression of CCR7, CD40 and IL12b. Applying these results towards an effective therapeutic modality, we developed a dual-transgene-armed MEM40 + IFNβ expressing conditionally replicative adenovirus (MEM-288) that simultaneously confers tumor-specific oncolysis and promotes tumor antigen release. MEM-288 drives MEM40 + IFNβ expression in freshly resected human lung tumors and generates potent anti-tumor responses as a monotherapy and in combination with immune checkpoint inhibitors. Furthermore, MEM-288 induced enhancement of tumor-reactive TILs and provides a rationale for studies to determine whether MEM-288 pre-treatment generates a superior TIL product for more effective adoptive T cell therapy. Citation Format: Hong Zheng, Scott Antonia, Mark J. Cantwell, Xiaoqing Yu, Amer A. Beg. Oncolytic adenovirus encoding transgenes for IFN-beta and recombinant CD40 ligand promotes conventional dendritic cell activation and trafficking with enhanced tumor infiltrating lymphocytes for effective cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3542.
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Audiger, Cindy, and Sylvie Lesage. "Merocytic dendritic cell: a new subset of conventional dendritic cells." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 118.11. http://dx.doi.org/10.4049/jimmunol.202.supp.118.11.
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Abstract Conventional dendritic cells (cDC) are potent antigen-presenting cells that induce the activation of naïve T cells in response to pathogens. cDC activity is mediated primarily by two cDC subsets, namely cDC1 and cDC2, each bearing unique properties. Recently, another DC subset, termed merocytic dendritic cells (mcDC), was defined. In contrast to both cDC1 and cDC2, mcDC are able to reverse T cell anergy, even in non-inflammatory conditions, properties that could be exploited to potentiate cancer treatments. Here, we further characterize mcDC to determine their relationship to cDCs. First, we demonstrate that mcDC express key cDC traits, namely they express the cDC-restricted transcription factor, Zbtb46, and are very potent inducers of mixed lymphocyte reactions. Second, transcriptomic studies reveal that mcDC are more closely related to cDC1 than to cDC2. In contrast, similar to cDC2, mcDC are dependent on IRF4, but not IRF8 and BATF3, two major transcription factors required for cDC1 differentiation. Third, investigating mcDC population dynamics in reconstitution kinetics studies and in parabiotic mice, we demonstrate that, as for cDC1 and cDC2, mcDCs are terminally differentiated cells. Altogether, these data demonstrate that mcDC compose novel cDC subset. Defining the properties of mcDC in mice may help identify a functionally equivalent subset in humans leading to the development of novel cancer immunotherapies.
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Bernardo, D., E. Arribas-Rodriguez, C. G. De Castro, A. Fiz-Lopez, A. De Prado, L. Fernandez-Salazar, J. Barrio, et al. "P067 Human intestinal CD103+SIRPα+ conventional dendritic cells from patients with Crohn′s disease prime IL-17+ T-cells." Journal of Crohn's and Colitis 16, Supplement_1 (January 1, 2022): i174. http://dx.doi.org/10.1093/ecco-jcc/jjab232.196.
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Abstract Background Crohn’s disease (CD) is a chronic inflammation of the human gastrointestinal tract. Intestinal conventional dendritic cells (cDC) maintain the balance between immunity against pathogens and tolerance towards nutrients and commensals. However, there is not much information about DC composition, phenotype and function in the human gut in CD. Methods Human intestinal resections were obtained from patients with ileocolonic CD and proximal colonic cancer. Both inflamed and non-inflamed tissue was obtained from the ileum and colon from CD patients. The non-affected tissue from the proximal (terminal ileum) and distal (proximal colon) sides of the colonic cancer resections (minimum 10cm distance from the tumor) constituted the reference tissue. Tissue was disaggregated and cDC and macrophages enriched by flow-sorting. Human intestinal cDC were identified within singlet viable leukocytes as CD14-CD64-HLA-DR+CD11c+. Type 1 cDC (cDC1) were defined as CD103+SIRPα- while type 2 cDC (cDC2) and identified as SIRPα+ and further divided into subsets based on the expression of CD103. Macrophages were identified within singlet viable leukocytes as CD14+CD64+HLA-DR+. All three cDC subsets and total macrophages were used to stimulate allogeneic CD4+ naïve T-cells which were further characterized by flow cytometry. Results All 3 human intestinal cDC subsets from non-CD controls were able to stimulate naïve T-cells as opposed to intestinal macrophages. Indeed, stimulated T-cells produced IL-10 and co-expressed FoxP3, being this capacity increased in both CD103+ subsets (CD103+SIRPα- and CD103+SIRPα+). Moreover, all three ileal cDC subsets stimulated T-cells more efficiently than their paired colonic counterparts, although the acquired T-cell profile did not differ among tissues. None of the cDC subets, on the contrary, induced the expression of IFNγ or IL-17 on stimulated T-cells. Referred to CD patients, all three colonic cDC subsets were more stimulatory than their counterparts from the control tissue, while CD103+SIRPα+ cDC from the inflamed ileum primed the generation of IL-17+ responding T-cells. Conclusion All human intestinal cDC subsets prime the generation of regulatory FoxP3+ and IL-10+ T-cells. This capacity was increased in both CD103+SIRPα- and CD103+SIRPα+, in agreement with the regulatory functions attributed to CD103+ cDC. All ileal cDC subsets were also more stimulatory than their colonic counterparts. Nevertheless, colonic cDC from CD patients were more stimulatory that non-CD controls, rendering CD103+SIRPα+ cDC from the inflamed tissue in CD with a higher capacity to generate Th17 cells, which suggests that their regulatory functions can be reshaped by the inflamed tissue microenvironment.
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Hori, T., and H. Spits. "Clonal analysis of human CD4-CD8-CD3- thymocytes highly purified from postnatal thymus." Journal of Immunology 146, no. 7 (April 1, 1991): 2116–21. http://dx.doi.org/10.4049/jimmunol.146.7.2116.
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Abstract Human triple-negative (CD4-CD8-CD3-) thymocytes purified from postnatal thymus by the use of magnetic bead columns and cell sorting were cultured in bulk or cloned with a feeder cell mixture of irradiated PBL, irradiated JY cells, and PHA. Triple-negative thymocytes proliferated well under these culture conditions, and after 12 days in bulk culture they remained triple negative. Limiting dilution experiments revealed that the frequency of clonogenic cells in fresh triple-negative thymocytes was less than 1%. Of 40 clones obtained in a representative experiment, 37 were triple negative and 3 were CD4+ TCR-alpha beta+. No TCR-gamma delta+ clones were isolated. Some of the triple-negative clones expressed CD16 and were apparently NK cells. Seven representative CD16-triple-negative clones were expanded and characterized in detail. These clones shared the common cell surface phenotype of CD1-CD2+CD3-CD4--CD8-CD5-CD7+CD16-CD56+. One of them expressed cytoplasmic CD3 delta and CD3 epsilon Ag, but these Ag were not detected in any peripheral blood-derived CD16- NK clones examined for comparison. The seven CD16- thymus-derived clones exhibited significant cytolytic activity against K562. The clone that expressed cytoplasmic CD3 Ag was shown to have the germ-line configuration of the TCR-beta and TCR-gamma genes. Thus, it is suggested that in vitro culture of triple-negative thymocytes can give rise to NK-like cells, including those that express cytoplasmic CD3 Ag. In contrast to previous reports, our results gave no evidence of differentiation of triple-negative thymocytes into TCR-alpha beta+ or TCR-gamma delta+ T cells.
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Terstappen, LW, S. Huang, and LJ Picker. "Flow cytometric assessment of human T-cell differentiation in thymus and bone marrow." Blood 79, no. 3 (February 1, 1992): 666–77. http://dx.doi.org/10.1182/blood.v79.3.666.666.
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Abstract Using multidimensional flow cytometry we have defined and quantified the human T-cell differentiation pathway, focusing on those events occurring among the most immature thymocytes and putative bone marrow (BM) T-precursors. Early thymocytes were found to express the CD34 antigen and consisted of a mean 1.2% of cells within human pediatric (n = 9) and 2.0% in fetal thymi (n = 4). All CD34+ thymocytes were atypical blast by morphology, expressed intracytoplasmatic, but not cell surface, CD3, and were cell surface CD2+, CD5+, CD7+, CD38+, CD45+, CD45RA+, CD49d+, and LECAM-1(Leu8)high. CD34high thymocytes lacked surface expression of CD4 and CD8, but as CD34 expression diminished there was a coordinate increase in CD4 levels, followed by the appearance of CD8. The expression of CD1 and CD10 also increased concomitant with the loss of CD34, whereas expression of LECAM-1 diminished with CD34 downregulation. The differential expression of these antigens on early thymocytes (as well as the number of thymocytes displaying these patterns) was highly reproducible among the nine pediatric and four fetal specimens examined, suggesting a precise, stereotyped regulation of early differentiation events. Cell populations with antigen expression patterns suggestive of pluripotent stem cell (CD34high, CD38-), or non-T-lineage committed stem cells (CD34+, CD33+ or CD34+, CD19+) were not identified in either fetal or pediatric thymi (sensitivity = 1/10(4)). The presence of cells with the antigenic profile of the earliest CD34+ thymocytes was explored in human BM. Putative BM T-cell precursors with the appropriate phenotype (CD34+, CD7+, CD5+, CD2+, LECAM-1high) were readily identified in fetal specimens (constituting +/- 2% of the CD34+ population), but could not be reliably detected in adults. In contrast with thymi, only 13% of these cells expressed cytoplasmatic CD3, suggesting the presence of the immediate precursor of the putative prothymocyte population. This was further supported by the detection of CD34bright, CD7+, CD2-, CD5-, LECAM-1moderate cells in fetal specimens. Our results document the flow of cell surface differentiation during T-lymphopoiesis and suggest that T-lineage features are first acquired in the BM. The ability to reproducibly identify and isolate T-cell precursor populations of precisely defined maturational stage in marrow and thymus by multiparameter flow cytometry will facilitate characterization of the molecular events controlling T-lineage differentiation.
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&NA;. "CDC." Oncology Times 25, no. 12 (June 2003): 20–21. http://dx.doi.org/10.1097/01.cot.0000289827.16457.1d.
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STUMP, ELIZABETH. "CDC." Neurology Today 8, no. 16 (August 2008): 20. http://dx.doi.org/10.1097/01.nt.0000337662.75151.23.
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Ellis, Fay. "CDC." Neurology Today 12, no. 22 (November 2012): 13. http://dx.doi.org/10.1097/01.nt.0000423167.85335.bf.
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Tessari, Anna, Isabella Testa, Elena Verzoni, Giovanni Nigita, Maurizio Colecchia, Dario Palmieri, Paolo Grassi, et al. "Gene-expression profiling of collecting duct carcinoma of the kidney." Journal of Clinical Oncology 34, no. 2_suppl (January 10, 2016): 540. http://dx.doi.org/10.1200/jco.2016.34.2_suppl.540.
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540 Background: Collecting duct carcinoma (CDC) of the kidney is a rare tumor, originating from renal medulla, characterized by younger age at diagnosis and poor prognosis. Since targeted therapies are currently not available for CDC, we aimed to identify the most deregulated pathways in this type of cancer to gain insights into new molecular targets. Methods: Total RNA was extracted from FFPE samples of primary CDC (n=9), clear cell carcinoma (CCC, n=7) and healthy normal (n=7) adjacent renal tissues (23 total samples). Gene expression profile was performed by GeneChip Human Transcriptome Array 2.0 (HTA 2.0 -Affymetrix). The One-Way between-subject ANOVA algorithm was used to calculate statistical significances of pairwise comparisons. Transcripts with a linear fold change (f.c.) of <-2/>2 (p-value<0.05) were included in the study. Functional enrichment analysis identified the most deregulated pathways in CDC. Results: A total of 1,079 genes (827 coding, 252 non-coding) were significantly deregulated comparing CDC, CCC and normal kidney (p<0.05). In CDC vs normal tissue comparison, 484 genes (339 coding, 145 non-coding) are significantly up-regulated, and 49 (40 coding, 9 non-coding) down regulated in tumors (p<0.05). The 4 most highly expressed transcripts in CDC are currently unknown, requiring further studies. Among the most altered known transcripts, we identified FN1 (f.c. 6.33), miR-21 (f.c. 4.01), KNG1 (f.c. -9.4) and AQP2 (f.c. -6.03), whose deregulation was previously associated with advanced disease and lower survival in renal cancer, supporting the quality of our analysis. Functional enrichment analysis indicated a strong downregulation of transcripts associated with histone modifications, function of cytoplasmic ribosomal proteins, senescence, autophagy and focal adhesion in CDC vs both CCC and normal tissues. Conclusions: Our analysis identifies several coding and non-coding transcripts differentially expressed in CDC vs CCC and normal kidney, resulting in alteration of a number of cellular pathways associated with cancer pathogenesis, progression and prognosis. These results pave the way to a deeper understanding of a rare tumor as CDC, driving the development of new, targeted therapies for this aggressive disease.
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Miranda, Paulo Sérgio C., Andrés Marco, Joan Arthur Caylà, Hernando Galdós-Tangüis, and Patricia García de Olalla. "Validation of four AIDS-case definitions in HIV-infected intravenous drug users in Barcelona, Spain." Revista Brasileira de Epidemiologia 1, no. 2 (August 1998): 170–76. http://dx.doi.org/10.1590/s1415-790x1998000200007.
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The objective of the study is to assess the sensitivity and specificity of four epidemiological AIDS-Case Definitions (CDC-87, CDC-93, Europe-93 and Revised Caracas) in HIV-infected intravenous drug users (IDU). The authors carried out a cross-sectional study with 136 IDUs, HIV-infected from a Men Penitentiary Center and from a drug addiction treatment center of Barcelona, Spain, between October/93 and April/94. A protocol, including demographic, clinical and laboratory variables was used by one doctor and the laboratory tests were done in the same institution. After that, the patients were classified in the four Epidemiological AIDS-Case Definitions used by this study. As gold standard we used the CD4 Cell Count (out point 200 or 14% CD4+). The number of AIDS cases varied between 31 and 84 according to the type of AIDS definition. The CDC-93 AIDS definition implied an increase of 170.9% in the number of cases in relation to CDC-87 AIDS-Case Definition. The sensitivities of the CDC-87, CDC-93, Europe-93 and Revised Caracas Epidemiological AIDS - Case Definitions were 34.2, 88.6, 45.6 and 56.9% while the specificities were 93.0, 75.4, 75.4 and 77.2%, respectively. The positive predictive values were between 72.0% (Europe-93) and 87.1% (CDC-87) and the negative predictive values were between 50.0% (Europe-93) and 82.7% (CDC-93). The authors concluded: the sensitivity and specificity of Caracas Revised Epidemiological AIDS-Case Definition was better than Europe-93 AIDS Case Definition. So this Definition can be very useful in countries and situations where the CD4 Cell Count is not available for technical or economical reasons.
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Stadnisky, Michael, Xuefang Xie, Ebony Coats, Timothy Bullock, and Michael Brown. "Self MHC class I licensed NK cells enhance adaptive CD8 T cell viral immunity (154.5)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 154.5. http://dx.doi.org/10.4049/jimmunol.186.supp.154.5.
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Abstract MHC class I (MHC I) is essential to NK and T cell effector and surveillance functions. However, it is unknown if MHC I polymorphism influences adaptive immunity through NK cells. Previously, we found that MHC I Dk, a cognate ligand for the Ly49G2 inhibitory receptor, was essential to NK control of murine (M)CMV infection. Here we assessed the significance of NK inhibitory receptor recognition of MCMV on CD8 T cells in genetically defined MHC I Dk disparate mice. We observed that Dk-licensed Ly49G2+ NK cells stabilized and then enhanced conventional dendritic cells (cDC) recovery following infection. Further, licensed NK support of cDC recovery was essential to enhance the tempo, magnitude and effector activity of virus-specific CD8 T cells. Minimal cDC and CD8 T cell number differences after low dose MCMV in Dk disparate animals further implied that licensed NK recognition of MCMV imparted qualitative cDC changes to enhance CD8 T cell priming.
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Tamiolakis, Demetrio, Ioannis Venizelos, Athanasia Kotini, Sylva Nikolaidou, and Nikolaos Papadopoulos. "Prevalence of CD8/CD4 Ratio in the Fetal Thymic Parenchyme in Down’s Syndrome." Acta Medica (Hradec Kralove, Czech Republic) 46, no. 4 (2003): 179–82. http://dx.doi.org/10.14712/18059694.2019.30.
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Aim: The maturation of most T- lymphocyte precursors takes place within the meshwork of thymic epithelial cells. Different steps of this process can be defined by immunologic phenotyping. The prothymocytes are positive for the terminal deoxynucleotidyl transferase (TdT) and give rise to cortical thymocytes, which express CD1, CD2, CD3, CD5, and both CD4 and CD8. These CD4 and CD8 double-positive cortical thymocytes differentiate into two lineages: CD4+ or CD8+ lymphocytes of the thymic medulla, by the tenth week of gestation. Our study points towards the determination of the CD8 cytotoxic/suppressor capacity of the fetal thymus in Down’s syndrome. Experimental design: A quantitative comparison of T-lymphocytes (CD3, CD4, and CD8) in the thymic parenchyme in embryos after voluntary abortion during 2nd trimester of gestation and embryos with Down’s syndrome, respectively, was performed. Results: Our results showed: 1) A statistically significant depletion in the total number of T-cells (CD3 positive) in the cases of embryos with Down’s syndrome over those after voluntary abortion, during the second trimester of gestation (p<0.0001, t-test). 2) A significant difference in the CD8/CD4 ratio in the cases of embryos with Down’s syndrome, during the second trimester of gestation which was numerically stronger with the progress of fetal development (20th week: p<0.025; 24th week: p<0.01, chi-square). Conclusions: The occurrence of increased CD8/CD4 ratio in the cases with Down’s syndrome, in the second trimester of gestation, underlines the cytotoxic / suppressor property of the thymus in the affected fetuses.
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Ribeiro, Camila Bastos, Jéssica Cristina dos Santos, Jacyelle Medeiros Silva, Pedro Henrique Silva de Godoi, Marta Regina Magalhães, Mônica Spadafora-Ferreira, Simone Gonçalves Fonseca, and Irmtraut Araci Hoffman Pfrimer. "Crotalus durissus collilineatus Venom Induces TNF-α and IL-10 Production in Human Peripheral Blood Mononuclear Cells." ISRN Inflammation 2014 (January 19, 2014): 1–7. http://dx.doi.org/10.1155/2014/563628.
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Snake venom has been the subject of numerous studies in an attempt to find properties and biological effects that may be beneficial to man. In this study we evaluated in vitro the effects of Crotalus durissus terrificus (Cdt) and Crotalus durissus collilineatus (Cdc) venom in human peripheral blood mononuclear cells (PBMCs). At 24 h, a significant decrease of viable cells was observed in cells stimulated with the Cdc venom at 0.0005 mg/mL and 0.005 mg/mL compared to the negative control. At 48 h, a significant decrease of viable cells was observed only in cells stimulated with Cdc venom at 0.005 mg/mL. A significant increase of TNF-α and IL-10 was detected 48 hours after culture of PBMC with Cdc, but not with Cdt venom. The expression of CD69 and PD1 (programmed death-1), activation and regulatory cell markers, on CD8+ and CD8− T cells did not change in the presence of Cdt and Cdc venom. Our results suggest the presence of proinflammatory and anti-inflammatory components in the Cdc venom. Further analysis should be done to identify those Cdc venom components as it has been done for the Cdt venom by other authors, indicating that modulatory components are found in the venom of different species of Crotalus snakes.
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Reddy, A. C., and K. S. Reddy. "Pediatric Patient With Neurological And Leukemic Peripheral Blood Involvement By Small Cell Variant Of ALK- Positive Anaplastic Large Cell Lymphoma (ALCL): Case Study." American Journal of Clinical Pathology 154, Supplement_1 (October 2020): S113—S114. http://dx.doi.org/10.1093/ajcp/aqaa161.248.
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Abstract Casestudy Anaplastic large cell lymphoma (ALCL), is a T-cell lymphoma typically consisting of large lymphoid cells including characteristic horseshoe- shaped hallmark cells. The rare small cell morphological variant of ALCL may pose a challenge in diagnosis, especially when the initial presentation is unusual. Results Our patient, a 7-year-old girl presented with a headache. A complete blood count showed leukocytosis and anemia. The smear was reported to have segmented neutrophils, reactive lymphocytes, and monocytes. A spinal tap was performed and flow analysis identified a minute aberrant T cell population (0.3% of total), positive for CD3, CD4, bright CD7; negative CD5, CD8 in the CSF sample. The peripheral blood sample was reviewed again; some small- medium atypical lymphocytes, with irregular nuclear contours and cytoplasmic azurophilic granules were noted. Flow immunophenotyping displayed an aberrant T cell population positive for CD45, CD2, CD3, bright CD7, CD4, CD13; negative CD30, TdT CD5, CD8, CD117, CD34; consistent with T cell lymphoma/leukemia. A cell block prepared from peripheral blood sample showed blood with numerous atypical cells with irregular nuclei positive for ALK, CD30, CD3, CD4, CD7; negative CD5 and CD8. A diagnosis of leukemic ALK(+) ALCL was rendered, though classic hallmark cells were difficult to see. A marrow biopsy showed interstitial and sinusoidal pattern of mainly small to medium-sized cells with irregular nuclei. Molecular study revealed ALK gene alteration showing characteristic NPM1-ALK fusion. The patient underwent a bone bone marrow transplantation but recently relapsed with a submandibular lymph hode biopsy showing the presence of many larger ALCL cells. Conclusion Correct clinical diagnosis of the small-cell variant of ALCL is often challenging as the scarce “hallmark cells” are scattered and difficult to recognize. While leukemic peripheral blood involvement is rare in ALCL, an association has been reported with small-cell variants, which may be a potential explanation for the poor prognosis and aggressive nature of small-cell variant ALCL. A meticulous examination of peripheral blood smears, comprehensive immunophenotypic studies, and early bone marrow and lymph node/tissue biopsy are needed to facilitate diagnosis.
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Komolafe, O. O., M. B. Adewole, and O. J. Matthew. "Assessment of Different Biochar and Composted Cow Dung on Soil Properties, Growth and Cob Weight of Maize." Journal of Tropical Crop Science 9, no. 02 (June 27, 2022): 124–36. http://dx.doi.org/10.29244/jtcs.9.02.124-136.
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Crop production in tropical soils is constrained by low fertility. The scarcity and high prices of chemical fertilizers have added to the existing challenges. This study examined the influence of different types of biochar and cow dung compost (CDC) on soil properties, growth and cob weight of maize. A polythene pot experiment was conducted at the screen house of the Institute of Ecology, Obafemi Awolowo University, Ile-Ife, Nigeria. The experiment was laid out in a completely randomized design. Amendments used were: cow dung compost, cow dung biochar and maize cob biochar, which were applied singly at the rates of 0, 4, 8, 12, 16 t.ha-1. The production of biochar from cow dung compost and maize cobs was done using a local charcoal-fired reactor. The feedstocks were slowly pyrolyzed at 350 0C and removed after 3hrs. The treatments were replicated twice. Soils amended with CDC had the highest growth parameters compared to other amendments. In the first season, CDC had a 22% increase in height compared to MCB. CDC had a height of 72 cm while MCB had the lowest height with 56 cm. The growth rate was as follows: CDC > CDB > MCB. CDC also increased cob weights when compared to other amendments. At 4 t ha-1, CDC had 2.20 g, CDB had 0.90 g while MCB had 0.47 g. Significant differences were observed among the treatments. However, it was observed that CDB increased soil chemical properties compared to other amendments. Soil properties such as organic carbon and total nitrogen were significantly improved in soils treated with CDB. This study concluded that cow dung biochar was better suited to improve soil properties while also improving crop growth compared to other amendments.
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Hucl, Pierre, and Maria Matus-Cádiz. "CDC EMDR-4, CDC EMDR-9, and CDC EMDR-14 spring wheats." Canadian Journal of Plant Science 82, no. 2 (April 1, 2002): 411–13. http://dx.doi.org/10.4141/p01-114.
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Early-maturing spring wheat germplasm lines CDC EMDR-4, CDC EMDR-9, and CDC EMDR-14 have high levels of seed dormancy. Their agronomic performance is comparable to that of the cultivar Columbus. These three lines had similar grain protein concentration and kernel hardness relative to the check cultivars, except CDC EMDR-4, which had a soft endosperm texture. Key words: Triticum aestivum L., germplasm, seed dormancy, pre-harvest sprouting resistance
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Bertho, JM, MD Mossalayi, AH Dalloul, G. Mouterde, and P. Debre. "Isolation of an early T-cell precursor (CFU-TL) from human bone marrow." Blood 75, no. 5 (March 1, 1990): 1064–68. http://dx.doi.org/10.1182/blood.v75.5.1064.1064.
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Abstract CD2-CD3-CD4-CD8- human bone marrow (BM) cells were previously shown to generate T-cell clones in vitro. This capacity was abolished after treatment of this population with anti-CD7 monoclonal antibody and complement. In this study, using rosetting with sheep erythrocytes, complement-dependent cytotoxicity, and specific immunoadherence method, we isolated a minor BM subset that contained more than 80% CD7+CD2-CD3- CD4-CD8- cells with small lymphoid cell morphology. They comprised most early T-cell precursors (CFU-TL) as they displayed high capacity to generate T-cell clones when cultured in limiting dilutions. CFU-TL nature of these cells was also confirmed by the sequential expression of mature T-cell specific markers on their surface after in vitro induction. This BM subset also contained 2% to 3% CFU-GM precursors. Together, these results pointed to the existence of BM CD7+CD2- precursors with high differentiation potential and showed the commitment of most of them to T-cell lineage.
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Bertho, JM, MD Mossalayi, AH Dalloul, G. Mouterde, and P. Debre. "Isolation of an early T-cell precursor (CFU-TL) from human bone marrow." Blood 75, no. 5 (March 1, 1990): 1064–68. http://dx.doi.org/10.1182/blood.v75.5.1064.bloodjournal7551064.
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CD2-CD3-CD4-CD8- human bone marrow (BM) cells were previously shown to generate T-cell clones in vitro. This capacity was abolished after treatment of this population with anti-CD7 monoclonal antibody and complement. In this study, using rosetting with sheep erythrocytes, complement-dependent cytotoxicity, and specific immunoadherence method, we isolated a minor BM subset that contained more than 80% CD7+CD2-CD3- CD4-CD8- cells with small lymphoid cell morphology. They comprised most early T-cell precursors (CFU-TL) as they displayed high capacity to generate T-cell clones when cultured in limiting dilutions. CFU-TL nature of these cells was also confirmed by the sequential expression of mature T-cell specific markers on their surface after in vitro induction. This BM subset also contained 2% to 3% CFU-GM precursors. Together, these results pointed to the existence of BM CD7+CD2- precursors with high differentiation potential and showed the commitment of most of them to T-cell lineage.
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Shaheen, M., L. Warmke, and M. Nassiri. "Focal Myositis with CD8+T-Cell predominance: an Inflammatory Myositis Mimicking a Soft Tissue Neoplasm." American Journal of Clinical Pathology 158, Supplement_1 (November 1, 2022): S109. http://dx.doi.org/10.1093/ajcp/aqac126.231.
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Abstract Introduction/Objective FM is a rare self-limiting T-cell rich lesion arising within muscles of young adults as a solitary lesion and can be confused with a variety of neoplastic/inflammatory conditions or lymphoma. Here we describe a rare T-cell rich variant of FM with CD8 predominance. Methods/Case Report A 51-year-old female presented with two-month history of left trapezius swelling. MRI showed an enhancing tumor within the muscle, suspicious of sarcoma, less likely myeloma. Results (if a Case Study enter NA) Biopsy showed diffuse infiltration of small lymphocytes in a fibrotic background and atrophic skeletal muscle. These lymphocytes stained positive for CD2, CD3, CD7, CD8, CD5 (partial), TIA1 (partial), CD43, CD57 and negative for CD4, CD30, CD56, CD57, granzyme B, perforin, BCL-6, BCL-2, Pax5, TCL1, and CD56. Ki-67 was (<10%) with few background CD20+ B cells. By flow cytometry, the CD8+ T-cells co-express CD2, CD3, CD7, with dim CD5 expression. TCR gene rearrangement study by PCR showed no clonal TCR Gamma gene rearrangement. Conclusion FM is extremely rare with only 22 cases well-described in the literature, all predominantly composed of CD4+ T-cells, clinically concerning for low-grade sarcomas, as inflammatory myofibroblastic tumor, inflammatory leiomyosarcoma, or liposarcoma. Careful analysis is essential for correct diagnosis. Mimics include other causes of myositis, such as polymyositis and inclusion body myositis. Depending on the extent of lymphocytic infiltrate, gene rearrangement studies might be necessary to rule out clonality. Recognition of this rare entity with excellent prognosis is crucial to provide appropriate management and avoid unnecessary, aggressive procedures.
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Diao, Jun, Jun Zhao, Anastassia Mikhailova, and Mark Cattral. "Identification of a novel immunosuppressive DC subpopulation in tolerized heart allografts (145.23)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 145.23. http://dx.doi.org/10.4049/jimmunol.184.supp.145.23.
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Abstract The role of dendritic cells (DC) in the maintenance of allograft tolerance is unclear. We analyzed the composition and function of DC infiltrates in tolerized murine heart allografts. Methods. B6 donor splenocytes (Day -7) plus anti-CD4 antibody (Day -1, 2 5 and 7) were injected into BALB/c recipients of B6 heart allografts; mice with heart grafts beating > 80 days were considered tolerant. Syngenic heart grafts (B6 to B6) were used as control. Results: We found that graft-infiltrating Lin-CD11c+MHCII+ cDC contained a novel Gr-1+ cDC subpopulation. B220+CD11c+MHCII+ plasmacytoid DC (pDC) were undetectable. In contrast to allograft Gr-1- cDC, which resemble typical immature tissue cDC, Gr-1+ cDC express lower levels of MHC class II and CD11c, adhere to culture plates, exhibit resistance to maturation stimuli, and stimulate allogeneic lymphocytes poorly. Gr-1+ cDC are distributed uniquely in tolerant allografts but not syngenic grafts or acutely rejecting allografts. Gr-1+cDC are absent in lymphoid tissues. Our previous studies have shown that the cytokine milieu of tumors skews pre-cDC differentiation towards Gr-1+ cDC. We found that pre-cDC exist in heart allografts. It remains to be determined whether tolerized hearts promote pre-cDC to differentiate into Gr-1+ cDC in situ. Conclusion: Tolerized allografts contain an immunosuppressive DC subpopulation that may contribute to the maintenance of long-term allograft survival.
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Araujo, Maria das Graças Pereira, Victor lima Soares, Alessandra Suelen Jardim Silva, Gustavo Henrique de Medeiros Oliveira, Lenilton Silva DA Silva Júnior, Hugo Henrique de Freitas Ferreira, Rodrigo Villar Freitas, et al. "Importance of Flow Cytometry in the Diagnosis of Sezary Syndrome in the State of Rio Grande Do Norte, Brazil." Blood 136, Supplement 1 (November 5, 2020): 39–40. http://dx.doi.org/10.1182/blood-2020-143378.
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Introduction:Sézary Syndrome (SS) is a leukemic form of Fungal Mycosis (FM), a rare form of T-cell lymphoma, characterized by erythroderma, generalized lymphadenopathy and infiltration of neoplastic T cells (Sézary cells) with cerebriform nucleus on the skin, lymph nodes and peripheral blood, being observed predominantly in men and individuals over the age of 60 and black. In the diagnosis of SS / FM, at least one of the criteria must be observed: minimum absolute Sézary cells count of 1000/mm3, expansion of TCD4+ cells with a ratio CD4/CD8 >10, loss of at least one mature T cell antigens as CD2, CD3, CD5, CD7 and CD26 in associated with increased lymphocyte count with evidence of a clone of circulating TCD4 cells determined by flow cytometry (CF).Objective:To investigate MF/SS in patients diagnosed with cutaneous lymphoma by CF immunophenotyping. Methodology: Were investigated in samples of peripheral blood (SP) from 11 patients of both sexes with initial history of MF and confection of SS due to the presence of Sézary cells by cytomorphological analysis by CF constituted by a panel of conjugated monoclonal antibodies (AcMo) to fluorochromes and targeted to T lymphocytes: CD1a, CD2, CD3, CD5, CD7, subpopulation T-Helper (CD3+/CD4+) and T-cytotoxic (CD3+/CD8+), in addition to TCR a/b and TCR g/d; Natural Killer cells: CD16-56; B lymphocytes: CD19, CD20, CD21, CD22, CD23, IgM, IgG, IgD anti-kappa and anti-lambda, in addition to CD10, TdT, CD103, CD25, CD38 and CD138, CD45 and CD14. At the same time, a complete blood count with differential white blood cell count and investigation of clinical and demographic data such as age, sex and ethnicity/race were also performed. Results: Of the patients analyzed, 6/11 were male, the age group above 60 years and white individuals were also found in 6/11 patients. The blood count showed lymphocytosis in 9/11 patients with the presence of convoluted cells in all cases. The diagnosis of SS was confirmed by the presence of Sezary cells in PB counting above 1000/mm3, with an immunophenotype confirmed by the predominance of TCD4+ lymphocytes (CD4/CD8 ratio > 10.0), associated with the expression of CD5, CD2, TCR a/b, CD3 weakly expressed. CD7 was absent in 10/11 samples analyzed. Antigens related to B lymphocytes and NK cells were absent in neoplastic cells as well as CD10, TdT and CD1a.Conclusions:SS is a leukemic variant of FM, characterized by exfoliative erythroderma, associated with lymphadenopathy and leukemization of FM with the appearance of Sézary cells in PB. Because it is a rare and essential disease, an accurate diagnosis of these diseases is necessary, and FC is an important diagnostic confirmation tool for SS. Disclosures No relevant conflicts of interest to declare.
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Granichin, O. N. "48th and 49th international conferences “decision and control” (IEEE CDC/CCC 2009 and CDC 2010)." Automation and Remote Control 72, no. 12 (December 2011): 2578–82. http://dx.doi.org/10.1134/s0005117911120125.
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Rasmussen, R. A., S. L. Counts, J. F. Daley, and S. F. Schlossman. "Isolation and characterization of CD6- T cells from peripheral blood." Journal of Immunology 152, no. 2 (January 15, 1994): 527–36. http://dx.doi.org/10.4049/jimmunol.152.2.527.
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Abstract Antibodies to the CD6 Ag have been described as having pan-T cell reactivity. We have recently demonstrated, however, that after treatment of PBL with an anti-CD6-blocked ricin-conjugated immunotoxin, clonal populations of CD3+, CD6- cells can be identified. Herein we show that through dual parameter staining of freshly isolated E-rosette+ cells, an average of 5 to 6% of either CD3+ or CD5+ cells express little or no CD6 on their surface. After negative selection by antibody-coated paramagnetic bead depletion, expanded CD6- T cells were shown to be CD1a-, CD2+, CD3+, CD5+, CD16-, CD56-, TCR-gamma/delta-, and consisted of both CD4+ and CD8+ cells. Furthermore, staining of digitonin permeabilized cells showed no cytoplasmic expression of the CD6 Ag and CD6 mRNA was not detected by Northern blot analysis. Identical staining patterns were observed for T cell clones isolated through bead depletion or immunotoxin treatment and expanded with either PHA or immobilized anti-CD3 mAb. It was also found that, relative to unfractionated T cells, the surface expression of CD5 was significantly diminished on CD6- T cells. Functionally, freshly isolated CD6- T cells showed substantially reduced alloreactivity in MLR compared with unfractionated E-rosette+ cells, yet both gave similar proliferative responses to either PHA or soluble tetanus toxin Ag. We conclude that there exists a minor subpopulation of mature T cells in peripheral blood that lack CD6. The diminished alloreactivity of these cells may help to explain the low incidence of graft-vs-host disease, despite high levels of engraftment, that has been reported in allogeneic bone marrow transplant patients receiving marrow treated with anti-CD6 (T12) mAb plus C'.