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Tian, Yamin, Seiichiro Kobayashi, Nobuhiro Ohno, Masamichi Isobe, Mayuko Tsuda, Yuji Zaike, Nobukazu Watanabe, Kenzaburo Tani, Arinobu Tojo et Kaoru Uchimaru. « Leukemic T Cells Are Specifically Enriched In a Unique CD3dimCD7low Subpopulation of CD4+ T Cells In Acute-Type Adult T Cell Leukemia ». Blood 116, no 21 (19 novembre 2010) : 4144. http://dx.doi.org/10.1182/blood.v116.21.4144.4144.
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Abstract Abstract 4144 [Background] Adult T-cell leukemia (ATL) is a malignant disorder caused by human T-cell leukemia virus type I (HTLV-I). Morphological discrimination of leukemic cells from non-leukemic T cells is often difficult in ATL since ATL cells reveal morphological diversity except for typical “flower cells”. Although a study using CD3 gating in flow cytometry reported that ATL cells were distinguishable as a CD3low population from normal lymphocytes, these cells were not well characterised as ATL cells. Considering that defective expression of CD7 as well as CD3 is common in ATL cells, we applied multi-color flow cytometry to detect a putative leukemia-specific cell population in the peripheral blood from ATL patients. [Methods and Results] (1) In flow cytometry, after dead-cell and monocyte removal, CD4+ T lymphocytes were gated on the CD3 versus CD4 plot. Based on cell density and fluorescence intensity of CD3 and CD7 in this population, we designated three subpopulations on this plot: CD3highCD7high, CD3dimCD7dim and CD3dimCD7low(Results of a representative ATL and a control sample are shown in Figure). The proportion of the CD3dim/CD7low subpopulation was significantly higher in acute-type ATL CD4+ lymphocytes than in normal controls(Figure). (2) To extensively characterise this subpopulation, we next estimated the HTLV-I proviral load by quantitative real-time PCR after FACS sorting based on this CD3 versus CD7 plot. In all patient samples, HTLV-I proviral integration was detected in all subpopulations. However, the proviral load was significantly higher in the CD3dim/CD7low subpopulation compared to the CD3high/CD7high subpopulation. Almost all of the cells in the CD3dim/CD7low subpopulation were HTLV-I infected. (3) We next examined CCR4 and CD25 expression in each subpopulation. Both CCR4 and CD25 expression levels were maintained at very low and similar levels throughout all subpopulations in normal control cells and in the CD3high/CD7high subpopulation of patients with ATL as well. In contrast, CCR4 expression was significantly up-regulated in CD3dim/CD7low subpopulation of patients with ATL compared to the CD3high/CD7high subpopulation (MFI: 36.5±17.2 vs. 3.8±1.1). The expression of CD25 was also up-regulated in the subpopulation (MFI: 7.8±8.0 vs. 2.7±1.6). (4) Monoclonal expansion of HTLV-I-infected cells in the CD3dim/CD7low subpopulation was indicated by the genomic integration site analysis using a long inverse polymerase chain reaction (PCR) method. (5) We reviewed the glass-slide specimens of FACS-sorted samples to evaluate the morphology of each subpopulation on the CD3 versus CD7 plot. Atypical lymphocytes with morphology such as a notch in the nucleus were observed in all subpopulations. The majority of sorted cells from CD3dim/CD7low subpopulation showed “flower cell”-like morphology. (6) We also detected a small CD3dim/CD7dim subpopulation other than the CD3dim/CD7low and CD3high/CD7high subpopulations in all patients with acute-type ATL who were analysed(Figure). This subpopulation contained the same clone as the CD3dim/CD7low subpopulation, although a phenotypical difference existed between these subpopulations. [Conclusion] (1) Above findings indicate that leukemic T cells are specifically enriched in a unique CD3dim/CD7low subpopulation of CD4+ T cells in acute-type ATL. This multi-color FACS system may be useful for precisely monitoring disease during chemotherapy, detecting minimal residual disease and analysing ATL cells. (2) Previous reports have revealed that HTLV-I-infected cells transform through multi-step oncogenesis. Detailed analysis of these three subpopulations (CD3high/CD7high, CD3dim/CD7dim and CD3dim/CD7low) may give some insight into oncogenesis of HTLV-I-infected cells. Disclosures: No relevant conflicts of interest to declare.
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Phillips, S. M., D. Walker, S. K. Abdel-Hafez, G. P. Linette, B. L. Doughty, P. J. Perrin et N. el Fathelbab. « The immune response to Schistosoma mansoni infections in inbred rats. VI. Regulation by T cell subpopulations. » Journal of Immunology 139, no 8 (15 octobre 1987) : 2781–87. http://dx.doi.org/10.4049/jimmunol.139.8.2781.
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Abstract These studies assess the roles of subpopulations of T lymphocytes in inducing and modulating resistance to Schistosoma mansoni. CDF rats were depleted of RT 7.1+ (anti-Pan-T), W3/25+ (anti-T helper/inducer), or OX8+ (anti-T suppressor) cells by the in vivo administration of monoclonal antibodies (mAb). The development of parasites and immunity to challenge by S. mansoni were compared with results in undepleted normal and congenitally athymic rats. Discrete subpopulations of T lymphocytes were adoptively transferred to ascertain effects upon parasite development and the protective immune response. In vitro studies, involving utilizing cocultivation of cell subpopulations +/- cyclosporin A, were utilized to dissect mechanisms. Depletion of T lymphocytes by anti-RT7.1 mAb and anti-W3/25 mAb resulted in augmented initial worm development, suboptimal resistance, and decreased antibody and delayed-type hypersensitive reactivity directed against schistosome antigens. Depletion with OX8 mAb produced opposite effects. The adoptive transfer of T cell subpopulations produced concordant results with T cell regulation expressed B cell-dependent effector mechanisms. The coadoptive transfer of cells resulted in the suppression of resistance afforded by the W3/25+ cells by OX8+ cells, which could be augmented in vitro by cyclosporin A. Thus, protective immunity to S. mansoni in rats is regulated by discrete subpopulations of T lymphocytes. The findings suggest the possibility of selective immune regulation of resistance based on the manipulation of specific T cell subpopulation.
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Kanof, Marjorie E. « Purification of T Cell Subpopulations ». Current Protocols in Immunology 00, no 1 (décembre 1991) : 7.3.1–7.3.5. http://dx.doi.org/10.1002/0471142735.im0703s00.
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Kubick, Norwin, Patrick C. Henckell Flournoy, Ana-Maria Enciu, Gina Manda et Michel-Edwar Mickael. « Drugs Modulating CD4+ T Cells Blood–Brain Barrier Interaction in Alzheimer’s Disease ». Pharmaceutics 12, no 9 (16 septembre 2020) : 880. http://dx.doi.org/10.3390/pharmaceutics12090880.
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The effect of Alzheimer’s disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. CD4+ T cells could both exacerbate and reduce AD symptoms based on their infiltrating subpopulations. Proinflammatory subpopulations such as Th1 and Th17 constitute a major source of proinflammatory cytokines that reduce endothelial integrity and stimulate astrocytes, resulting in the production of amyloid β. Anti-inflammatory subpopulations such as Th2 and Tregs reduce inflammation and regulate the function of Th1 and Th17. Recently, pathogenic Th17 has been shown to have a superior infiltrating capacity compared to other major CD4+ T cell subpopulations. Alzheimer’s drugs such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda) are known to play an important part in regulating the mechanisms of the neurotransmitters. However, little is known about the effect of these drugs on CD4+ T cell subpopulations’ infiltration of the brain during AD. In this review, we focus on understanding the influence of AD drugs on CD4+ T cell subpopulation interactions with the BBB in AD. While current AD therapies improve endothelial integrity and reduce astrocytes activations, they vary according to their influence on various CD4+ T cell subpopulations. Donepezil reduces the numbers of Th1 but not Th2, Rivastigmine inhibits Th1 and Th17 but not Th2, and memantine reduces Th1 but not Treg. However, none of the current AD drugs is specifically designed to target the dysregulated balance in the Th17/Treg axis. Future drug design approaches should specifically consider inhibiting CD4+ Th17 to improve AD prognosis.
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Leonhardt, U., U. Wagner, M. Werner et L. Engelmann. « T-cell-subpopulations in septic patients ». Critical Care 5, Suppl 1 (2001) : P059. http://dx.doi.org/10.1186/cc1127.
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Ferrara, Andrea, Marvin M. McMillen et Garth H. Ballantyne. « T-cell subpopulations and colorectal cancer ». Diseases of the Colon & ; Rectum 33, no 5 (mai 1990) : 367–69. http://dx.doi.org/10.1007/bf02156259.
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Abramova, A. V., I. V. Galtseva, E. A. Mikhailova, N. M. Kapranov, Yu O. Davydova, Z. T. Fidarova, V. V. Troitskaya, E. N. Parovichnikova et V. G. Savchenko. « Oligoclonality and subpopulation structure of bone marrow T-cells in patients with aplastic anaemia ». Russian journal of hematology and transfusiology 65, no 4 (10 décembre 2020) : 417–30. http://dx.doi.org/10.35754/0234-5730-2020-65-4-417-430.
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Introduction. The main pathogenetic mechanism of the development of aplastic anemia (AA) is a violation of the immune regulation of hematopoiesis.Aim: to study of the subpopulation composition of T-cells and the repertoire of the T-cell receptor in AA patients.Patients and Methods. The study included AA patients (n = 40) without prior immunosuppressive therapy in 2018–2020. The T-cell subpopulation structure and T-cell receptor Vβ-family (TCR-Vβ) oligoclonality were studied in samples of bone marrow using flow cytometry.Results. We report characteristic properties of T-cell subpopulations of bone marrow in all AA patients: elevated counts of cytotoxic T-cells, effector CD4+ and CD8+ cells, CD4+ memory cells, which may suggest a long-term antigenic stimulation with subsequent activation of these cell subpopulations resulting in hyperexpression of pro-inflammatory cytokines. Diminishing of naive CD4+ and CD8+ cells, regulatory and double negative T-cells may indicate a relaxing control of cytokine-producing T-cells. A relationship has been established between the AA severity and counts of effector, regulatory, double negative and PD-1 positive T-cells. A highest count of potentially cytokine-producing T-cells and lowest count of cells involved in T-cell activity regulation were observed in very severe AA patients. Studies of the TCR-Vβ repertoire revealed oligoclonal expansion in the cytotoxic T-cell subpopulation.Conclusion. Enrichment in selected Vβ families suggests autoreactive T-cell clonality and attests to the immune nature of AA. A dynamic TCR-Vβ repertoire assay may be recommended in the disease monitoring. Flow cytometry helps identify valuable biomarkers for T-cell clone monitoring in AA and a better assessment of the disease progression.
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Hafler, D. A., D. A. Fox, D. Benjamin et H. L. Weiner. « Antigen reactive memory T cells are defined by Ta1. » Journal of Immunology 137, no 2 (15 juillet 1986) : 414–18. http://dx.doi.org/10.4049/jimmunol.137.2.414.
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Abstract Ta1 is a 105,000 dalton protein that is weakly expressed on a small fraction of resting human peripheral blood T cells but strongly expressed in vitro on T cell clones and a substantial proportion of activated T cells. Unlike receptors for growth factors such as IL 2, the Ta1 antigen is present on T cell lines and clones irrespective of cell cycle. The function of Ta1 was investigated after separation of T lymphocytes into Ta1-enriched and Ta1-depleted subpopulations that were obtained from normal human subjects. Although Ta1-enriched T cells constitute only 10 to 15% of the E rosette-positive lymphocyte population, most, if not all, of the anamnestic response to the recall antigens tetanus toxoid and mumps reside in the Ta1+ population. Both Ta1-enriched and -depleted cells responded equally well to the mitogen PHA. The autologous mixed lymphocyte response was also greater in the Ta1-enriched subpopulation but not to the degree seen with soluble antigen. Increased proliferation was not due simple to increased inducer cell function within the Ta1+ subpopulations because both Ta1- and Ta1+ cells induced similar amounts of Ig synthesis in the presence of PWM. Additionally, increasing numbers of Ta1- cells did not suppress the enhanced proliferative responses of Ta1+ cells, and thus Ta1- cells do not appear to be functioning as suppressor cells. The Ta1 antigen appears to be a marker for previously activated T cells in peripheral blood, and this subpopulation appears to include T memory cells.
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SKÖLD, RYTTER, IVARS et CARDELL. « Characterization of Subpopulations of T-Cell Receptor Intermediate (TCRint) T Cells ». Scandinavian Journal of Immunology 49, no 6 (juin 1999) : 611–19. http://dx.doi.org/10.1046/j.1365-3083.1999.00535.x.
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Bertrand, F. E., L. G. Billips, G. L. Gartland, H. Kubagawa et H. W. Schroeder. « The J chain gene is transcribed during B and T lymphopoiesis in humans. » Journal of Immunology 156, no 11 (1 juin 1996) : 4240–44. http://dx.doi.org/10.4049/jimmunol.156.11.4240.
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Abstract In mice and chickens, J chain appears to be expressed only in activated B cells and plasma cells. In humans, studies based mainly on transformed cells suggest that J chain expression may initiate during earlier stages in B lineage differentiation. In the present study, we isolated a series of hematopoietic subpopulations from human fetal and adult tissues by immunofluorescence cell sorting and examined each subpopulation for J chain expression by reverse transcriptase-PCR. In fetal and adult bone marrow, J chain transcripts were detected at all stages of B lineage differentiation, including the progenitor (CD34+/CD19-) and pro-B (CD34+/CD19+) cell subpopulations. J chain mRNA was also detected during fetal thymocyte development: double negative (CD4-/CD8-) through single positive (CD4+ or CD8+) cell subpopulations. The J chain message was not detected in peripheral CD3+ T cells, CD14+ monocytes, and CD56+ NK cells from either fetal or adult samples. The nucleotide sequence of J chain PCR products from CD34+/CD19- bone marrow progenitors and CD4+/CD8- thymocytes proved identical to the previously reported sequence of functionally spliced J chain mRNA. These results suggest that the J chain gene is transcriptionally active during early stages of both B cell and T cell differentiation, before the expression of their respective Ag receptors.
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Baldwin, Cynthia, et Chuang Chen. « Gamma delta T cell subpopulations defined by expression of distinct sets of the co-receptor WC1 genes. (89.6) ». Journal of Immunology 184, no 1_Supplement (1 avril 2010) : 89.6. http://dx.doi.org/10.4049/jimmunol.184.supp.89.6.
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Abstract Gamma delta T cells can be 60% of peripheral blood mononuclear cells in young ruminants with the majority expressing the WC1 co-receptor. WC1 co-receptors are composed of up to eleven extracellular scavenger receptor (SRCR) domains with the interdomain pattern organized as a-[b-c-d-e-d’]-[b-c-d-e-d’] and the greatest differences occurring in the most distal domain 1 (‘a’ in the pattern). Two main subpopulations are defined by the presence of either the WC1.1 or the WC1.2-antigenic epitopes and these are functionally distinct since only a small subpopulation of WC1.1+ cells proliferate to antigens of Leptospira and produce IFN-γ in response to leptospira or IL-12. Prior to the onset of the studies described here the copy number of WC1 genes and the WC1 forms that account for the serologically-defined WC1.1 and WC1.2 were unknown. By applying real-time QPCR and relative quantification analysis, 13 WC1 domain 1 genes were found to be present in cattle from two breeds. In addition, we found 6 subpopulations of WC1+ γδ T cells defined by anti-WC1 subpopulation-specific mAbs and showed that this correlated with expression of different sets of WC1 genes. The studies described here demonstrate that more than one WC1 gene is expressed on a single WC1+ γδ T cells, that specific WC1 genes are associated with γδ T cell subpopulations defined by a panel of anti-WC1 subpopulation-specific mAbs and that these differences are likely to influence their response to various stimuli.
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Katsura, Y., T. Amagai, T. Kina, T. Sado et S. Nishikawa. « Two subpopulations of stem cells for T cell lineage. » Journal of Immunology 135, no 5 (1 novembre 1985) : 3021–27. http://dx.doi.org/10.4049/jimmunol.135.5.3021.
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Abstract An assay system for the stem cell that colonizes the thymus and differentiates into T cells was developed, and by using this assay system the existence of two subpopulations of stem cells for T cell lineage was clarified. Part-body-shielded and 900-R-irradiated C57BL/6 (H-2b, Thy-1.2) recipient mice, which do not require the transfer of pluripotent stem cells for their survival, were transferred with cells from B10 X Thy-1.1 (H-2b, Thy-1.1) donor mice. The reconstitution of the recipient's thymus lymphocytes was accomplished by stem cells in the donor cells and those spared in the shielded portion of the recipient that competitively colonize the thymus. Thus, the stem cell activity of donor cells can be evaluated by determining the proportion of donor-type (Thy-1.1+) cells in the recipient's thymus. Bone marrow cells were the most potent source of stem cells, the generation of donor-derived T cells being observed in two out of 14 recipients transferred with as few as 1.5 X 10(4) cells. The stem cell activity of spleen cells was estimated to be about 1% of that of bone marrow cells, and no activity was found in thymus cells. By contrast, when the stem cell activity was compared between spleen and bone marrow cells of whole-body-irradiated (800 R) C57BL/6 mice reconstituted with B10 X Thy-1.1 bone marrow cells by assaying in part-body-shielded and irradiated C57BL/6 mice, the activity of these two organs showed quite a different time course of development. Spleen cells showed a markedly high level of activity 7 days after the reconstitution, followed by a decline, whereas the activity of bone marrow cells was very low on day 7 and increased crosswise. The results strongly suggest that the stem cells for T cell lineage in the bone marrow comprise at least two subpopulations, spleen-seeking and bone marrow-seeking cells. Such patterns of compartmentalization of stem cells in the spleen and bone marrow of irradiated recipients completely conform to the general scheme of the relationship between restricted stem cells and less mature stem cells, including pluripotent stem cells, which became evident in other systems such as in the differentiation of spleen colony-forming cells or of stem cells for B cell lineage.
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Tedder, T. F., M. D. Cooper et L. T. Clement. « Human lymphocyte differentiation antigens HB-10 and HB-11. II. Differential production of B cell growth and differentiation factors by distinct helper T cell subpopulations. » Journal of Immunology 134, no 5 (1 mai 1985) : 2989–94. http://dx.doi.org/10.4049/jimmunol.134.5.2989.
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Abstract Two monoclonal antibodies (HB-10 and HB-11), which react with human T, B, and NK cells, identify approximately 50% of the Leu-3+ T helper (TH) cells in adult blood. In the present studies, the functional capabilities of the HB-11+ and HB-11-TH cell subpopulations were examined after purification by fluorescence-activated cell sorting. Both subpopulations proliferated in response to PHA, Con A, PWM, and OKT-3 antibodies. The HB-11+ TH cells gave a minimal proliferative response to soluble tetanus toxoid antigen, whereas HB-11-TH cells responded well. After mitogen activation, both HB-11+ and HB-11-TH cells and to produce soluble factors which induce large B cells to proliferate. However, PWM-stimulated HB-11+TH cells were incapable of inducing B cells to differentiate into antibody-secreting plasma cells, whereas HB-11-TH cells were efficient in this regard. The results suggest that the HB-11 antigen is expressed on a subpopulation of virgin TH cells that can produce B cell growth factors but are deficient in the ability to produce B cell differentiation factors.
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Kim, Young-Hee, Tae-Young Jung, Shin Jung, Woo-Youl Jang, Kyung-Sub Moon, In-Young Kim, Min-Cheol Lee et Je-Jung Lee. « Tumour-infiltrating T-cell subpopulations in glioblastomas ». British Journal of Neurosurgery 26, no 1 (27 juin 2011) : 21–27. http://dx.doi.org/10.3109/02688697.2011.584986.
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Haudebourg, Thomas, Nicolas Poirier et Bernard Vanhove. « Depleting T-cell subpopulations in organ transplantation ». Transplant International 22, no 5 (30 octobre 2008) : 509–18. http://dx.doi.org/10.1111/j.1432-2277.2008.00788.x.
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Eedy, D. J., D. Burrows, T. Clifford et A. Fay. « Elevated T cell subpopulations in dental students ». Journal of Prosthetic Dentistry 63, no 5 (mai 1990) : 593–96. http://dx.doi.org/10.1016/0022-3913(90)90082-n.
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Salami, Falastin, Lampros Spiliopoulos, Marlena Maziarz, Markus Lundgren, Charlotte Brundin, Rasmus Bennet, Magnus Hillman, Carina Törn et Helena Elding Larsson. « Long-Term GAD-alum Treatment Effect on Different T-Cell Subpopulations in Healthy Children Positive for Multiple Beta Cell Autoantibodies ». Journal of Immunology Research 2022 (25 mai 2022) : 1–17. http://dx.doi.org/10.1155/2022/3532685.
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Objective. The objective of this study was to explore whether recombinant GAD65 conjugated hydroxide (GAD-alum) treatment affected peripheral blood T-cell subpopulations in healthy children with multiple beta cell autoantibodies. Method. The Diabetes Prevention–Immune Tolerance 2 (DiAPREV-IT 2) clinical trial enrolled 26 children between 4 and 13 years of age, positive for glutamic acid decarboxylase autoantibody (GADA) and at least one other autoantibody (insulin, insulinoma antigen-2, or zinc transporter 8 autoantibody (IAA, IA-2A, or ZnT8A)) at baseline. The children were randomized to two doses of subcutaneously administered GAD-alum treatment or placebo, 30 days apart. Complete blood count (CBC) and immunophenotyping of T-cell subpopulations by flow cytometry were performed regularly during the 24 months of follow-up posttreatment. Cross-sectional analyses were performed comparing lymphocyte and T-cell subpopulations between GAD-alum and placebo-treated subjects. Results. GAD-alum-treated children had lower levels of lymphocytes (109 cells/L) ( p = 0.006 ), T-cells (103 cells/μL) ( p = 0.008 ), T-helper cells (103 cells/μL) ( p = 0.014 ), and cytotoxic T-cells (103 cells/μL) ( p = 0.023 ) compared to the placebo-treated children 18 months from first GAD-alum injection. This difference remained 24 months after the first treatment for lymphocytes ( p = 0.027 ), T-cells ( p = 0.022 ), T-helper cells ( p = 0.048 ), and cytotoxic T-cells ( p = 0.018 ). Conclusion. Our findings suggest that levels of total T-cells and T-cell subpopulations declined 18 and 24 months after GAD-alum treatment in healthy children with multiple beta-cell autoantibodies including GADA.
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Kalavska, Katarina, Zuzana Sestakova, Andrea Mlcakova, Paulina Gronesova, Viera Miskovska, Katarina Rejlekova, Daniela Svetlovska et al. « Detection of Specific Immune Cell Subpopulation Changes Associated with Systemic Immune Inflammation–Index Level in Germ Cell Tumors ». Life 12, no 5 (2 mai 2022) : 678. http://dx.doi.org/10.3390/life12050678.
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The tumor microenvironment (TME) and the host inflammatory response are closely interconnected. The interplay between systemic inflammation and the local immune response may influence tumor development and progression in various types of cancer. The systemic immune–inflammation index (SII) represents a prognostic marker for germ cell tumors (GCTs). The aim of the present study was to detect specific immune cell subpopulation changes which were associated with the SII level in chemotherapy-naïve GCT patients. In total, 51 GCT patients, prior to cisplatin-based chemotherapy, were included in the present study. Immunophenotyping of peripheral blood leukocyte subpopulations was performed using flow cytometry. The SII level was correlated with the percentage of various leukocyte subpopulations. The obtained results demonstrated that SII levels above the cut-off value of SII ≥ 1003 were associated with higher neutrophil percentages. An inverse correlation was found between the SII and the peripheral lymphocyte percentage that logically reflects the calculations of the SII index. Furthermore, the presented data also showed that in the lymphocyte subpopulation, the association with the SII was driven by T-cell subpopulations. In innate immunity–cell subpopulations, we observed a correlation between SII level and neutrophils as well as associations with eosinophil, basophil, natural killer cell and dendritic cell percentages. We suppose that the described interactions represent a manifestation of cancer-induced immune suppression. The results of the present study contribute to the elucidation of the interrelationship between tumor cells and the innate/adaptive immune system of the host.
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Witte, P. L., et J. W. Streilein. « Development and ontogeny of hamster T cell subpopulations. » Journal of Immunology 137, no 1 (1 juillet 1986) : 45–54. http://dx.doi.org/10.4049/jimmunol.137.1.45.
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Abstract The Syrian hamster is unique among laboratory animals because products of class I MHC genes are monomorphic. Thus, this species may be a model in which to test the relationship between MHC polymorphism and the T cell antigen receptor repertoire. Recently, cytotoxic and helper T cell subpopulations have been distinguished on the basis of cell surface phenotype detected with monoclonal antibodies (mAb). We used these reagents (mAb 110 detects all peripheral T cells and mAb 38 detects cytotoxic T cells) to dissect and categorize thymic populations according to relative maturational status. The two mAb divide thymocytes into four subpopulations in the young adult. Two (110+ 38+, 110+ 38-) were peripheral-like and were housed in the medulla, exclusively; another subset (110- 38+) consisted almost entirely of TdT+ cortical thymocytes. The fourth subset (110- 38-), bearing neither marker, was heterogeneous and consisted mostly of medium-large-size thymocytes, including cells with an early phenotype (nuclear TdT+). Cells with the cortical phenotype proved to be the most sensitive to cortisone treatment, whereas those which expressed the medullary marker, 110, were most resistant. To ascertain the relationship between 110- and 110+ T lineage cells, we followed the appearance of the four thymic subpopulations during ontogeny of the hamster thymus. Adult-like thymic architecture (delineation of cortex and medulla) as well as the two 110- subsets were established before expression of 110 antigen was apparent in the thymus. However, lymphocytes bearing the 110 antigen were found in lymph nodes prior to thymus during ontogeny, concomitant with developing T cell function in peripheral tissue. This finding implies that cells lacking 110 antigen were exported from the thymus and subsequently acquired expression of the molecule in the periphery, and we suggest that acquisition of 110 antigen may be a stage of postthymic maturation. Although 110+ cells appeared to be the most mature subset by several criteria, all functional thymocytes of adults or neonates were not 110+. Thus, we conclude that the 110 marker is acquired after T cells reach functional maturity. Moreover, the response profile of isolated 38+ thymocytes was analogous to peripheral 38+ T cells, suggesting that the dichotomy of function detected with our mAb also occurs before acquisition of 110 antigen. We have modeled what is known about hamster T cell development into a hypothetical scheme.
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Öbro, Nina Friesgaard, Lars Peter Ryder, Hans Ole Madsen, Mette Klarskov Andersen, Birgitte Klug Albertsen, Peder Skov Wehner, Steen Rosthoej et al. « Intra-Tumoral Blast Heterogeneity and Implications for Minimal Residual Disease Detection in T-Cell Acute Lymphoblastic Leukemia ». Blood 124, no 21 (6 décembre 2014) : 1076. http://dx.doi.org/10.1182/blood.v124.21.1076.1076.
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Abstract Introduction:The early treatment response, measured as minimal residual disease (MRD), is the most important tool for treatment stratification in T-cell acute lymphoblastic leukemia (T-ALL). Flow cytometry-based MRD (Flow-MRD) monitoring, in addition to the PCR-MRD method, is often important to ensure a sensitive MRD marker. Additionally, Flow-MRD investigation may add biological information to the MRD result itself, and allow cell sorting for biological and functional analyses. Flow-MRD in T-ALL consists of identification of cells with immature T-cell phenotype in bone marrow. However, important pitfalls in Flow-MRD, e.g. treatment-related marker modulation and intra-tumoral immunophenotypic heterogeneity, are poorly described. The aim of this study was to explore the implications of these pitfalls on T-ALL MRD detection and on the concordance between the two MRD methods. Potentially both PCR- and Flow-MRD methods might miss blast subpopulations, which is important if subpopulations have divergent chemosensitivity. Methods:The patient cohort included 49 Danish T-ALL patients (1-45 years of age) treated according to the NOPHO ALL2008 protocol. Standard PCR- and flow cytometry-based MRD data were obtained as part of routine MRD monitoring. We investigated intra-tumoral heterogeneity of the leukemia-associated immunophenotype by flow cytometry (diagnostic BM samples), including clonal T-cell receptor gene-rearrangements in flow-sorted blast subpopulations (22 patients). Immunophenotypic MRD markers (including assessment of modulation) were re-evaluated at follow-up in MRD-positive patients. Flow-MRD was validated by PCR-MRD analysis in flow-sorted cell populations (61 follow-up BM samples, 32 patients). Results:At diagnosis, more than 80% of the T-ALL patients had a heterogeneous immunophenotype, most often involving CD1a, CD4, and TdT. The degree of overall heterogeneity, as defined by the number of markers with heterogeneous expression showing distinct blast subpopulations, did not show association to day29 PCR-MRD. Except for one patient, the dominant T-cell receptor clonal gene rearrangements were conserved across phenotypically diverse blasts. Immunophenotypic changes in MRD-positive patients at early follow-up often included subpopulation-loss and/or marker down-modulation of CD1a, TdT and/or CD4. The marker modulations were frequently independent of each other in different subpopulations. Overall, flow cytometry-based identification of blasts and normal cells at Flow-MRD time points was verified by PCR in the flow-sorted cells: In patients where at least 90% of the blasts showed aberrant marker expression at diagnosis, the flow-sorted MRD cells were concordantly PCR-positive, and flow-sorted phenotypically normal cells were similarly PCR-negative in all but three samples that had very high MRD levels (>20%). However, many patients had only partly-informative immunophenotypes (less than 90% of blasts having aberrant marker). Three discrepant cases with Flow-MRD underestimation showed loss of CD1a- and TdT and down-modulation of CD99, verified in flow-sorting experiments. Conclusions and Discussion: We show that intra-tumoral immunophenotypic heterogeneity—a possible result of genetic instability—is common in T-ALL patients and involves several immaturity and T-linage markers commonly used in Flow-MRD. The dominant PCR-MRD targets are in most cases conserved across the diverse blast subpopulations at diagnosis, but in rare cases PCR-MRD might miss a subpopulation. The observed immunophenotypic changes in T-ALL blasts and blast subpopulations at early follow-up, including reduction of immaturity markers, represent important pitfalls in Flow-MRD. Flow-sorting experiments verified that, when all blasts of heterogeneous immunophenotypes were informative, MRD identified by flow cytometry at follow-up was highly concordant with PCR-MRD markers in sorted cells. The T-ALL blast heterogeneity and marker modulations, which are possibly treatment protocol-specific, are important to take into account to obtain reliable Flow-MRD and thus correct treatment stratification of T-ALL patients. Disclosures No relevant conflicts of interest to declare.
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Deveci, Figen, H. Handan Akbulut, Ilhami Celik, M. Hamdi Muz et Fulya İlhan. « Lymphocyte Subpopulations in Pulmonary Tuberculosis Patients ». Mediators of Inflammation 2006 (2006) : 1–6. http://dx.doi.org/10.1155/mi/2006/89070.
Texte intégralRésumé :
Protection againstMycobacterium tuberculosisis based on cell-mediated immunity, most importantly involvingCD4+andCD8+T-cell subsets. The aim of this study was to evaluateCD4+andCD8+T-cell profiles andCD19+andCD3-CD(16+56)+populations in patients with pulmonary tuberculosis.CD4+andCD8+T cells, B-lymphocytes, and natural killer (NK) cells were evaluated in 75 active (APTB) and 25 inactive (IPTB) pulmonary tuberculosis cases and 20 healthy subjects (HCs). The results were compared at different stages of antituberculosis treatment in the APTB patients and also according to X-ray findings in the newly diagnosed APTB patients. The percentages ofCD4+T cells were significantly lower(P<.01)and those ofCD3-CD(16+56)+cells were significantly higher(P<.01)in APTB patients than in HCs.CD8+T cells were significantly decreased(P<.05), andCD3-CD(16+56)+cells were significantly increased(P<.01), in IPTB patients compared to HCs. The percentages ofCD4+,CD8+,CD3-CD19+, andCD3-CD(16+56)+cells showed no differences at different times of the antituberculosis regimen, and different stages of newly diagnosed APTB patients. APTB patients have a reduced percentage of circulatingCD4+T cells and an increased percentage of NK cells compared with healthy individuals. These cells could play important roles in the immune response toM tuberculosisinfection.
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Cox, Charlotte Victoria, Paraskevi Diamanti et Allison Blair. « Assessing CD97 and CD99 As Markers of Leukaemia Initiating Cells in Paediatric ALL ». Blood 120, no 21 (16 novembre 2012) : 1882. http://dx.doi.org/10.1182/blood.v120.21.1882.1882.
Texte intégralRésumé :
Abstract Abstract 1882 Overall survival rates in paediatric acute lymphoblastic leukaemia (ALL) have dramatically improved but around 20% do not respond to current therapies and subsequently relapse. Leukaemia initiating cells (LIC) are the topic of much investigation, as these cells can self-renew and may have the potential to cause relapse. It has been shown that multiple subpopulations of ALL cells have the ability to initiate the disease in immune deficient mouse models. Therefore, treatment should be targeted at all cells with this capacity, if the disease is to be eradicated. Minimal residual disease (MRD) detection is an invaluable tracking tool to assess early treatment response and recent studies have highlighted potential markers that may improve the sensitivity of MRD detection by flow cytometry. CD97 and CD99 are two markers which were over expressed in paediatric ALL. Incorporating these markers into investigations of LIC may allow discrimination of leukaemia cells from normal haemopoietic stem cells (HSC). In this study we evaluated the expression of CD34 in combination with CD97 in B cell precursor (BCP) ALL cases and CD99 in T-ALL cases and subsequently assessed the functional capacity of the sorted subpopulations in vitro and in vivo. Ten ALL samples (6 B-ALL & 4 T-ALL) with a median age 7 years (range 2–15 years) were studied. One B-ALL case and 3 T-ALL cases were considered high risk by molecular assessment of MRD at day 28 of treatment. Flow cytometric analyses of the ALL samples and 8 normal haemopoietic cell samples demonstrated that both CD97 and CD99 were over expressed in ALL patients (78.9±14.8% & 76.4±32.8%, respectively) when compared to normal haemopoietic cells (14.1±25.4%; p=0.001, 47.1±10%; p=0.03, respectively). Cells were sorted for expression/lack of expression of these markers and proliferation of the sorted cells was assessed in suspension culture over a 6 week period. In the B-ALL patients the CD34+/CD97+ subpopulation represented the bulk of leukaemia cells (65.2±32.1%), the CD34−/CD97+ the smallest fraction (3.3±2.4%) with the CD34+/CD97− and CD34−/CD97− subpopulations representing 21.1±31.5% and 10.5±5.8% of cells, respectively. When the functional capacity of these subpopulations was assessed in vitro greatest expansion was observed in cells derived from CD34+/CD97− subpopulation (2–173 fold) from 9.4×103 at initiation up to 1.5×106 cells at week 6. Expansion was also observed, to a lesser extent in the CD34−/CD97− subpopulation (3.4–28 fold) from 8×103 up to 1.4×106 cells. No expansion was observed in cultures of CD34+/CD97+ and CD34−/CD97− subpopulations but cells were maintained throughout the culture period. These sorted subpopulations were also inoculated into NOD/LtSz-SCID IL-2Rγc null (NSG) mice to evaluate repopulating capacity. To date, engraftment has been achieved with 3 subpopulations; CD34+/CD97+ (3–28.8% CD45+), CD34+/CD97− (0.5–25.5% CD45+) and CD34−/CD97+ (23.8% CD45+) cells. When the functional capacity of T-ALL cases was assessed the CD34+/CD99+ subpopulation represented the bulk of cells at sorting (51.87±47.2%), the CD34+/CD99- subpopulation was the smallest (0.9±0.8%) and the CD34−/CD99+ and CD34−/CD99− subpopulations represented 32.1±38.9% and 27.2±33.4% of cells, respectively. Greatest expansion was observed in cultures of CD34+/CD99- cells (4.6–1798 fold) from 7.5×103 up to 2.6×106 cells at week 6. The other 3 subpopulations expanded to a lesser extent (1.3–216 fold) from 5×103 up to 1.8×106 cells. When the functional capacity of these cells was assessed in NSG mice, engraftment was achieved in all subpopulations; CD34+/CD99+ (87–90.5% CD45+), CD34+/CD99− (1.5–84.9% CD45+), CD34−/CD99+ (31.3–98.6% CD45+) and CD34−/CD99− (3–92.9% CD45+). In some cases, cells recovered from BM of NSG inoculated with CD99− cells had high expression of CD99, typical of the patient samples at diagnosis, indicating that the inoculated CD99− cells had differentiated in vivo. Studies are ongoing to assess the self-renewal capacity of these subpopulations by serial transplantation. The findings to date indicate that targeting CD97 and CD99, either alone or in combination with CD34 would not eliminate all cells with the capacity to initiate and maintain B-ALL and T-ALL, respectively. Further developments in therapy may require targeting leukaemogenic pathways, rather than only cell surface markers to improve survival outcome in paediatric ALL. Disclosures: No relevant conflicts of interest to declare.
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Tupitsyn, N. N., T. M. Dzhumanazarov, A. D. Palladina, A. K. Alakhverdiyev, S. V. Chulkova et P. V. Kononets. « IMMUNOLOGICAL PARAMETERS OF BONE MARROW IN NON-SMALL CELL LUNG CANCER ». Russian Journal of Biotherapy 19, no 2 (18 juin 2020) : 47–54. http://dx.doi.org/10.17650/1726-9784-2019-19-2-47-54.
Texte intégralRésumé :
Introduction Generation of most immunocompetent cells takes place in bone marrow Bone marrow. As well, bone marrow is a peripheral lymphoid organ where antitumor effector cells and memory cells are present. The aim of the work is to estimate peripheral lymphoid cell subpopulations in bone marrow of lung cancer patients. Materials and methods Study has been done in 68 pts with lung cancer: squamous cell cancer (n = 28), adenocarcinoma (n = 38), other forms (n = 2). In all cases standard diagnostic and staging procedures were performed, as well as morphological (myelogram) and immunological study of bone marrow lymphocyte subpopulations. Multicolor Flow cytomtry was used for study of bone marrow lymphocyte populations. We studied T-cells and its subpopulations, B-cells, NK-cells, perforin-positive cells, and CD27-positive cells. Results Squamous cell lung cancer was characterized by higher content of bone marrow mature T-cells (CD3), and CD8 lymphocytes. More typical for adenocarcinoma was mature B-cell reaction (CD20). Effector (perforin-positive) populations of lymphocytes also were related to histological type of cancer: for adenocarcinoma presence of CD4-positive cytotoxic lymphocytes and CD27-expression on effector cells. Perforin-containing lymphoid cells were in opposite correlation to erythrocaryocytes. Conclusion Subpopulational lymphocyte content of bone marrow is related to histological variant of cancer and erythropoiesis in lung cancer patients.
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Chen, Z. W., Z. C. Kou, C. Lekutis, L. Shen, D. Zhou, M. Halloran, J. Li, J. Sodroski, D. Lee-Parritz et N. L. Letvin. « T cell receptor V beta repertoire in an acute infection of rhesus monkeys with simian immunodeficiency viruses and a chimeric simian-human immunodeficiency virus. » Journal of Experimental Medicine 182, no 1 (1 juillet 1995) : 21–31. http://dx.doi.org/10.1084/jem.182.1.21.
Texte intégralRésumé :
Changes in T cell receptor (TCR) V beta repertoire and their correlation with virologic events were investigated in rhesus monkeys after acute infection with the simian immunodeficiency virus (SIV). 11 genetically defined rhesus monkeys were experimentally infected with SIVmac or a chimeric simian-human immunodeficiency virus (SHIV), and their peripheral blood lymphocytes (PBL) and lymph nodes were prospectively assessed for TCR V beta gene expression. PBL and lymph nodes of the acutely infected monkeys demonstrated an expansion of selected V beta-expressing T lymphocyte subpopulations as early as 3 d after infection. These expanded V beta-expressing lymphocyte subpopulations were comprised predominantly of CD8+ cells. Six of seven infected monkeys sharing a single electrophoretically defined major histocompatibility complex class I allele exhibited a similar expansion of V beta 14-expressing PBL. Sequence analyses of V-D-J segments of TCR-beta cDNA indicated that the V beta-expressing T cell subpopulation expansion can be oligoclonal. SIVmac-specific CD8+ cytotoxic T lymphocytes were demonstrated in both PBL and lymph nodes of the infected monkeys at the time expansion of the selected V beta-expressing cell subpopulations was seen. Finally, the expansion of the selected V beta-expressing lymphocytes in PBL coincided with the emergence and clearance of SIV p27 from the plasma of the infected monkeys. These results demonstrate that acute infection of rhesus monkeys with SIVmac or SHIV results in an expansion of CD8+ lymphocyte subpopulations expressing selected V beta gene families. The selectively expanded T lymphocytes may contribute to early viral clearance after acute SIVmac or SHIV infection.
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Riggs, J. E., A. M. Lussier, S. K. Lee, M. C. Appel et R. T. Woodland. « Differential radiosensitivity among B cell subpopulations. » Journal of Immunology 141, no 6 (15 septembre 1988) : 1799–807. http://dx.doi.org/10.4049/jimmunol.141.6.1799.
Texte intégralRésumé :
Abstract We have previously shown that low doses of ionizing radiation selectively impair a functionally defined B cell subpopulation. Normal mice, after exposure to 200 rad of ionizing radiation, have normal or near normal splenic plaque-forming cell responses to thymus-independent type 1 Ag, but reduced responses to thymus-independent type 2 Ag. Here, we confirm and extend the original findings by using hapten-specific serum RIA to demonstrate this differential radiosensitivity is systemic. We also examined splenocytes stained with a panel of lymphocyte surface Ag by FACS analysis to determine if these functional changes are accompanied by a physical alteration of the B cell pool of irradiated mice. Single-parameter FACS analyses demonstrate a diminution in both B cell number and the heterogeneity of membrane Ag expression within the surviving B cell pool after irradiation. In contrast, T cells are relatively radioresistant as the relative percentage of T cells in the irradiated splenocyte pool increases, whereas the heterogeneity of membrane Ag expression remains constant. Multiparameter FACS analyses indicate that B cells with the sIgM much greater than sIgD phenotype are more radiosensitive than B cells of the sIgM much less than sIgD phenotype. In addition, immunohistochemical analysis of splenic sections stained with anti-IgM or anti-IgD reveal the enhanced radiosensitivity of marginal zone B cells.
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Bohana-Kashtan, Osnat, Hyam Levitsky et Curt I. Civin. « Identification of New Alloantigen-Reactive CD8+ Cytotoxic and Suppressor T Cell Subpopulations. » Blood 110, no 11 (16 novembre 2007) : 3229. http://dx.doi.org/10.1182/blood.v110.11.3229.3229.
Texte intégralRésumé :
We sought to develop a better understanding of the T cells involved in the human allogeneic immune response, in order to eventually engineer a donor graft with reduced GVHD-mediating potential, without ablating general immune competence. Prior studies reported that all the activated CD4+ T cells responding to a specific antigen challenge reside within the CD4high population expressing high levels of membrane CD4. We identified a new population of activated CD8+ T cells that developed during an in vitro allogeneic immune response, along with the allo-activated CD4high T cell population. Analogous to activated CD4+ T cells, this new T cell population was distinguished by up-regulated CD8 (and CD38) expression (CD8highCD38+). In accordance with Martins et al. (Blood 2004, 104:3429), we found that the depletion of the CD4highCD38+ population resulted in reduced 2o response to the original 2nd party stimulators. In contrast, depletion of the CD8highCD38+ population resulted in an increased 2o response to 2nd party cells, with no change in the response to 3rd party or CMV antigens. Elevated numbers of CD8highCD38+ T cells potently reduced the 1o and 2o responses to 2nd party, but not to 3rd party cells or CMV antigens. The complementary, non-activated CD8normalCD38− T cell population had no inhibitory effect. Importantly, we found that CD8highCD38+ T cells mediated both a specific cytotoxic response (that could be inhibited by the pan-caspase inhibitor, Z-VAD), and a specific suppressive response toward the original 2nd party stimulators (that was not affected by Z-VAD), and within this CD8highCD38+ population, there was a subpopulation of cytotoxic T cells (perforin+LAMP1+CD56+CD11b+CD11c+) and a subpopulation of non-cytotoxic T cells. Furthermore, we found that although CD8highCD38+ T cells differentially expressed CD28, both CD8highCD38+CD28− and CD8highCD38+CD28− T cells mediated a cytotoxic as well as a suppressor T cell response toward the original 2nd party cells (different from the published suppressive function of CD8+CD28− T cells observed by Liu et al, Int Immunol 1998, 10:775). Upon separation of cytotoxic CD8highCD38+ T cells from suppressor CD8highCD38+ T cells, we will explore the GVHD potential of these 2 novel activated CD8high T cell subpopulations, in a sensitive in vivo xenograft model for GVHD using NOD/SCID/IL2Rγnull immunodeficient mice.
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Patrushev, Alexander V., Alexey V. Samtsov, Vladimir Yu Nikitin, Alexey V. Soukharev, Oksana P. Gumilevskaya et Irina A. Sukhina. « Assessment of CLA+T-cell subpopulations in the blood of patients with chronic dermatoses ». Vestnik dermatologii i venerologii 96, no 4 (17 novembre 2020) : 22–31. http://dx.doi.org/10.25208/vdv1155-2020-96-4-22-31.
Texte intégralRésumé :
Background. CLA+T-cell are an important component of skin-associated lymphoid tissue, and thus determine the pathogenesis of many immuno-mediated dermatoses.
Aims. Determine the relative number of CLA+T-cell subpopulations in the peripheral blood of patients with psoriasis, lichen planus and atopic dermatitis, as well as assess their impact on the severity of dermatoses.
Materials and methods. We examined 82 patients with psoriasis aged 19 to 62 years, 54 patients with lichen planus (LP) aged 18 to 54 years, 44 patients with atopic dermatitis (AD) aged 18 to 44 years, as well as 20 practically healthy individuals aged 18 to 52 years who were admitted to the clinic for the removal of benign skin neoplasms.
All patients underwent a standard clinical examination with the determination of indicators that characterize the severity of dermatosis: PASI (Psoriasis Area and Severity Index) for patients with psoriasis, IPSLP (index of prevalence and severity of lichen planus) for patients with lichen planus and SCORAD (Scoring of Atopic Dermatitis) for patients with atopic dermatitis. Defining subpopulations CLA+T-lymphocytes were carried out on a flow cytometer Cytomics FC500 by Beckman Coulter using appropriate combinations of direct monoclonal antibodies and isotopic controls. The groups were compared using the nonparametric Mann Whitney test, and the differences were considered significant at p0,05. To analyze the relationship between the severity of dermatosis and the relative content of subpopulations CLA+T-cells used Spearman's rank correlation coefficient.
Results. In patients with psoriasis, a significant increase in the percentage of the total number of T-lymphocytes positive for CLA (CLA+CD3+) and T-helpers positive for CLA (CLA+CD4+) (p=0,002 and 8,5104, respectively), in patients with PL and AD only CLA+CD4+ lymphocytes (p=0,028 and 0,003, respectively). In the progressive period of psoriasis, a direct moderate correlation was found between the circulating subpopulation of cytotoxic T lymphocytes positive for CLA (CLA+CD8+) and the PASI index (rs=0,47; p0,001), in the acute period of AD between the CLA+CD3+ subpopulations and CLA+CD4+ cells and the SCORAD index (rs=0,53; p 0,001 and rs=0,57; p0,001, respectively). In PL, the severity of the course of dermatosis was not accompanied by any significant changes in the CLA-positive T-cell subpopulations.
Conclusion. The results of the study confirmed the important role of CLA+T cell subpopulations in the development of chronic dermatoses. In all groups (psoriasis, LP and AD), an increase in the relative number of CLA+CD4+ T-helpers was noted compared with the control group. The relationship between the severity of psoriasis and the relative number of CLA+CD8+ cytotoxic T-lymphocytes, and the severity of AD with CLA+CD3+ and CLA+CD4+ T-helpers is also shown.
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Fyfe, G., J. A. Cebra-Thomas, E. Mustain, J. M. Davie, C. D. Alley et M. H. Nahm. « Subpopulations of B lymphocytes in germinal centers. » Journal of Immunology 139, no 7 (1 octobre 1987) : 2187–94. http://dx.doi.org/10.4049/jimmunol.139.7.2187.
Texte intégralRésumé :
Abstract With two new monoclonal antibodies and flow cytometry, we defined three subpopulations among B cells expressing binding sites for peanut agglutinin (i.e., B cells of the germinal center). On monoclonal antibody (5B5) binds globotriaosyl ceramide. The B lymphocytes binding 5B5 have binding sites for peanut agglutinin on the surface and express only small amounts of sIgD and sIgM. When tested against a panel of B cell lines, only Burkitt's lymphoma cells were 5B5+. Moreover, the 5B5+ cells have larger average sizes and a large fraction of proliferating cells. The other monoclonal antibody (HK23) binds a 90,000 protein. Lymphocytes binding HK23 are 5B5- and include T cells and a subpopulation of B cells. In contrast to 5B5+ cells, the HK23+ and peanut agglutinin positive B cells express a large amount of sIgM. These two subpopulations of germinal centers are distinct from the germinal center B cell subpopulation expressing the CD23 (Blast-2) antigen. The CD23+ B cells are 5B5- and express an intermediate level of HK23 antigen. In addition, CD23+ B cells are highly variable in number, whereas the proportions of HK23+ and 5B5+ cells are relatively stable.
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McLendon, Bryan A., Heewon Seo, Avery C. Kramer, Robert C. Burghardt, Fuller W. Bazer et Greg A. Johnson. « Pig conceptuses secrete interferon gamma to recruit T cells to the endometrium during the peri-implantation period† ». Biology of Reproduction 103, no 5 (27 juillet 2020) : 1018–29. http://dx.doi.org/10.1093/biolre/ioaa132.
Texte intégralRésumé :
Abstract The emerging paradigm in the immunology of pregnancy is that implantation of conceptuses does not progress in an immunologically suppressed environment. Rather, the endometrium undergoes a controlled inflammatory response during implantation as trophectoderm of elongating and implanting pig conceptuses secrete the pro-inflammatory cytokine interferon gamma (IFNG). Results of this study with pigs revealed: (1) accumulation of immune cells and apoptosis of stromal cells within the endometrium at sites of implantation during the period of IFNG secretion by conceptuses; (2) accumulation of proliferating cell nuclear antigen (PCNA)-positive T cells within the endometrium at sites of implantation; (3) significant increases in expression of T cell co-signaling receptors including programmed cell death 1 (PDCD1), CD28, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and inducible T cell co-stimulator (ICOS), as well as chemokines CXCL9, 10, and 11 within the endometrium at sites of implantation; (4) significant increases in T cell co-signaling receptors, PDCD1 and ICOS, and chemokine CXCL9 in the endometrium of cyclic gilts infused with IFNG; and (5) identification of CD4+ (22.59%) as the major T cell subpopulation, with minor subpopulations of CD8+ (1.38%), CD4+CD25+ (1.08%), and CD4+CD8+ (0.61%) T cells within the endometrium at sites of implantation. Our results provide new insights into the immunology of implantation to suggest that trophectoderm cells of pigs secrete IFNG to recruit various subpopulations of T cells to the endometrium to contribute to a controlled inflammatory environment that supports the active breakdown and restructuring of the endometrium in response to implantation of the conceptus.
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Savchenko, Andrey, Aleksandr Borisov, Igor Kudryavtsev et Anton Moshev. « RELATIONSHIP OF THE T-REGULATORY CELLS NUMBER WITH THE CYTOTOXIC T-LYMPHOCYTES AND NKT-CELLS LEVELS IN PATIENTS WITH RENAL CANCER ». Problems in oncology 63, no 1 (1 janvier 2017) : 104–9. http://dx.doi.org/10.37469/0507-3758-2017-63-1-104-109.
Texte intégralRésumé :
The aim of the study was to investigate the features of the relation to the number and the phenotype of the cytotoxic T-lymphocytes and NKT-cell from regulatory T-cells content in the blood by patients with renal cell carcinoma. The study included patients with renal cell carcinoma (T3N0M0, clear cell type) at the age of 40-55 years before surgery. Lymphocyte immunophenotyping was performed by flow cytometry. It is found that in the peripheral blood of the patients with renal cell carcinoma accompanied by increased number of T-regulatory cells observed decrease content of the cytotoxic T-lymphocytes and increased levels of the NKT-cells. It is assumed that no change in the number of activated T-regulatory cells and cytotoxic T-lymphocyte determined migration from the blood. Increasing the amount of the NKT-cells in renal cancer is determined by the increase of activated and effector cells but at lower levels of the regulatory subpopulation. The content of the T-regulatory cells in healthy people weakly correlated with the effector subpopulations of T-lymphocytes. In patients with renal cancer the number of the activated T-regulatory cells is closely correlated with the various NKT-lymphocytes fractions. Moreover, if the mature and regulatory NKT-cells subset detected negative relations, so with the NKT-cells expressing CD28 and CD57 markers found positive correlations that characterizes the codirectional dynamics the activated of the regulatory and effector T-lymphocyte subpopulations levels in the background of tumor growth. A canonical analysis demonstrated that the highest significance kidney cancer patients have activated regulatory T-cells, cytotoxic T cells and NKT-cells. A canonical analysis demonstrated that the highest significance by renal cancer patients have activated regulatory T-cells, cytotoxic T-cells and NKT-cells.
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Risley, Christopher A., Christopher D. Scharer, Jeremy M. Boss et Frances E. Lund. « T-bet expression marks a transcriptionally and functionally distinct population of memory B cells ». Journal of Immunology 206, no 1_Supplement (1 mai 2021) : 114.18. http://dx.doi.org/10.4049/jimmunol.206.supp.114.18.
Texte intégralRésumé :
Abstract Memory B cells (Bmem) rapidly differentiate and mount antibody (Ab) responses to previously encountered antigen (Ag). Mouse Bmem can be subdivided using BCR isotype or expression of CD73, CD80, and PD-L2. Many of these Bmem populations were discovered following vaccination with alum-adjuvanted Ag, which drives a distinct immune response from those generated after infection with IFN-inducing viruses. We previously demonstrated that the IFNγ-inducible transcription factor T-bet is required for Bmem recall responses to influenza but not nematode infections, suggesting that T-bet might regulate anti-viral Bmem. Therefore, we hypothesized that the anti-viral Bmem compartment likely contained cells that were distinct from the established subpopulations. Here, we show that T-bet expression within the flu-specific Bmem is heterogeneous and not restricted to any of the previously described Bmem subsets. Furthermore, B cell-intrinsic T-bet ablation caused the loss of one of these Bmem subpopulations, and inducible deletion of T-bet in Bmem caused the loss of the same subpopulation. To determine how T-bet regulates the Bmem compartment, we performed single-cell RNAseq and CITEseq on flu infection-induced Bmem. We identified numerous transcriptionally distinct clusters of Bmem, several of which express T-bet as well as genes associated with plasma cell function. Consistent with this, in vitro assays show that T-bet+ Bmem differentiate more robustly than T-betneg Bmem. These data show that the anti-viral Bmem compartment is heterogeneous and includes a T-bet expressing subpopulation that appears poised for rapid Ab responses. Thus, T-bet appears to be important for the maintenance and function of some, but not all, Bmem.
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Coser, Lilian de O., Lívia M. Genaro, Amauri S. Justo-Junior, Plínio Trabasso, Ricardo M. Pereira, Luciana P. Ruas et Maria HSL Blotta. « Evaluation of CD8+ T cell subpopulations in paracoccidioidomycosis ». Future Microbiology 16, no 13 (septembre 2021) : 977–85. http://dx.doi.org/10.2217/fmb-2020-0261.
Texte intégralRésumé :
Aim: We aimed to verify the frequency of CD8+ T cell subsets in patients with acute form and chronic form of paracoccidioidomycosis. Material & Methods: Mononuclear cells from paracoccidioidomycosis patients and healthy donors were isolated and phenotyped by flow cytometry. Dendritic cells were pulsed with Paracoccidioides brasiliensis yeast and co-cultures with lymphocytes. Cytokine production was measured by ELISA. Results: Acute form patients present a higher frequency of Tc1 and Tc10 cells, while chronic form patients have more Tc1 and Tc21 cells, compared with healthy controls. In vitro assays showed that P. brasiliensis induced polarization to the Tc17/Tc22 subsets. Conclusion: Our results suggest that CD8+ T cells can respond in a similar way to P. brasiliensis infection, regardless of the clinical presentation of the disease.
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Bhondeley, Manoj K., Raj D. Mehra, Narinder K. Mehra, Ashok K. Mohapatra, Prakash N. Tandon, Subimal Roy et Veena Bijlani. « Imbalances in T cell subpopulations in human gliomas ». Journal of Neurosurgery 68, no 4 (avril 1988) : 589–93. http://dx.doi.org/10.3171/jns.1988.68.4.0589.
Texte intégralRésumé :
✓ The quantitation of cells bearing CD3, CD4, CD8, and B cell phenotypic markers, as well as an estimation of serum immunoglobulin (Ig)G, IgA, and IgM, was carried out in a group of 39 glioma patients with different grades of malignancy. The findings were compared with those obtained from 21 normal healthy control subjects. The analysis revealed a significant decrease both in the absolute numbers and in the percentages of circulating CD3+ (p < 0.001) and CD4+ (p < 0.001) cells, while the CD8+ and Pan B+ cells remained within the normal range irrespective of the type and grade of tumor. The CD4+:CD8+ ratio was significantly decreased in all categories of patients. The CD4 lymphopenia was also evident in 10 patients who had no history of previous immunosuppressive drug therapy (steroids and anticonvulsants) until the commencement of the study. The Ig levels were within the normal range in patients with malignant astrocytoma and glioblastoma multiforme, whereas a three- and fourfold increase in the IgM level was observed in patients with astrocytoma. It is suggested that T cell lymphopenia in glioma patients could mainly be due to a selective depletion of CD4+ cells and that it occurs principally as a reaction to the tumor.
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Lascurain, Ricardo, Flor Porras, Renata Báez, Raúl Chávez, Salvador Martínez-Cairo, Georgina Alvarez et Edgar Zenteno. « Amaranthus leucocarpusLectin Recognizes Human Naive T Cell Subpopulations ». Immunological Investigations 26, no 5-7 (janvier 1997) : 579–87. http://dx.doi.org/10.3109/08820139709088542.
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&NA;. « BCG vaccinations in neonates affect T-cell subpopulations ». Inpharma Weekly &NA;, no 1520 (janvier 2006) : 20. http://dx.doi.org/10.2165/00128413-200615200-00052.
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FISHWILD, DIANNEE, et EDGAR G. ENGLEMAN. « Human T-Cell Subpopulations Distinguished by Monoclonal Antibodies ». International Ophthalmology Clinics 25, no 2 (1985) : 55–62. http://dx.doi.org/10.1097/00004397-198502520-00008.
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Gunduz, Kamer, Gunseli Ozturk, Ender Terzioglu et Filiz Sebik. « T Cell Subpopulations and IL-2R in Vitiligo ». Journal of Dermatology 31, no 2 (février 2004) : 94–97. http://dx.doi.org/10.1111/j.1346-8138.2004.tb00514.x.
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HOLEN, E., et S. ELSAYED. « Effects of β2adrenoceptor agonists on T-cell subpopulations ». APMIS 106, no 7-12 (juillet 1998) : 849–57. http://dx.doi.org/10.1111/j.1699-0463.1998.tb00231.x.
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Essunger, Paulina, et Alan S. Perelson. « Modeling HIV Infection of CD4+ T-cell Subpopulations ». Journal of Theoretical Biology 170, no 4 (octobre 1994) : 367–91. http://dx.doi.org/10.1006/jtbi.1994.1199.
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Achiron, A., M. Mendel, G. Rechavi, B. Ramot et E. Melamed. « Changes in T-cell subpopulations in multiple sclerosis ». Annals of Neurology 26, no 2 (août 1989) : 291–92. http://dx.doi.org/10.1002/ana.410260224.
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Mozzanica, Nino, Ugo Frigerio, Aldo F. Finzi, Angelo Cattaneo, Marco Negri, Franco Scaglione, Franco Fraschini et Sergio Foppa. « T cell subpopulations in vitiligo : A chronobiologic study ». Journal of the American Academy of Dermatology 22, no 2 (février 1990) : 223–30. http://dx.doi.org/10.1016/0190-9622(90)70029-h.
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Deuse, T., H. Reichenspurner, R. C. Robbins et S. Schrepfer. « 236 : Immunosuppressive Agents Differently Suppress T Cell Subpopulations ». Journal of Heart and Lung Transplantation 29, no 2 (février 2010) : S81. http://dx.doi.org/10.1016/j.healun.2009.11.247.
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Menzel, E. J., G. J. Zlabinger, A. Dunky et C. Steffen. « Autoimmunity and T-cell subpopulations in old age ». Archives of Gerontology and Geriatrics 7, no 4 (décembre 1988) : 249–60. http://dx.doi.org/10.1016/0167-4943(88)90008-8.
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Lecolier, B., S. Marion, F. Derouin, F. Daffos et G. Sarrot. « T-cell subpopulations of fetuses infected byToxoplasma gondii ». European Journal of Clinical Microbiology & ; Infectious Diseases 8, no 6 (juin 1989) : 572–73. http://dx.doi.org/10.1007/bf01967488.
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Sata, Fumihiro, Shunichi Araki, Takeshi Tanigawa, Yoko Morita, Susumu Sakurai, Akinori Nakata et Naochika Katsuno. « Changes in T Cell Subpopulations in Lead Workers ». Environmental Research 76, no 1 (janvier 1998) : 61–64. http://dx.doi.org/10.1006/enrs.1997.3790.
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Bacchus-Souffan, Charline, Mark Fitch, Jori Symons, Mohamed Abdel-Mohsen, Daniel B. Reeves, Rebecca Hoh, Mars Stone et al. « Relationship between CD4 T cell turnover, cellular differentiation and HIV persistence during ART ». PLOS Pathogens 17, no 1 (19 janvier 2021) : e1009214. http://dx.doi.org/10.1371/journal.ppat.1009214.
Texte intégralRésumé :
The precise role of CD4 T cell turnover in maintaining HIV persistence during antiretroviral therapy (ART) has not yet been well characterized. In resting CD4 T cell subpopulations from 24 HIV-infected ART-suppressed and 6 HIV-uninfected individuals, we directly measured cellular turnover by heavy water labeling, HIV reservoir size by integrated HIV-DNA (intDNA) and cell-associated HIV-RNA (caRNA), and HIV reservoir clonality by proviral integration site sequencing. Compared to HIV-negatives, ART-suppressed individuals had similar fractional replacement rates in all subpopulations, but lower absolute proliferation rates of all subpopulations other than effector memory (TEM) cells, and lower plasma IL-7 levels (p = 0.0004). Median CD4 T cell half-lives decreased with cell differentiation from naïve to TEM cells (3 years to 3 months, p<0.001). TEM had the fastest replacement rates, were most highly enriched for intDNA and caRNA, and contained the most clonal proviral expansion. Clonal proviruses detected in less mature subpopulations were more expanded in TEM, suggesting that they were maintained through cell differentiation. Earlier ART initiation was associated with lower levels of intDNA, caRNA and fractional replacement rates. In conclusion, circulating integrated HIV proviruses appear to be maintained both by slow turnover of immature CD4 subpopulations, and by clonal expansion as well as cell differentiation into effector cells with faster replacement rates.
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Damani-Yokota, Payal, Jancie C. Telfer et Cynthia L. Baldwin. « Variegated expression of members of the WC1 pathogen recognition receptor and co-receptor multi-gene family on γδ T cells ». Journal of Immunology 196, no 1_Supplement (1 mai 2016) : 216.22. http://dx.doi.org/10.4049/jimmunol.196.supp.216.22.
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Abstract Cells of the immune system recognize disease-causing pathogens and respond in a manner to stop the infection. While we know how conventional cells of the immune system do this, for some non-conventional cells such as γδ T cells this process is less clear. We have shown that bovine γδ T cells bear lineage-specific transmembrane glycoproteins, known as WC1, are coded by a multigenic family and that these molecules function both as pattern recognition receptors (PRR) and signaling co-receptors for cellular activation. For example, while a subpopulation known as WC1.1+ γδ T cells respond early and participate in a recall response to the spirochetes Leptospira interrogans and Leptospira borgpetersenii, other subpopulations that express a different set of the WC1 genes do not respond. Other experiments showed that WC1 molecules on γδ T cells that respond to Leptospira bind the bacteria and are involved in cell activation. Thus, we hypothesize that WC1 is essential for the recognition of bacterial pathogens by γδ T cells and that the WC1 family members expressed by a particular cell will determine its ability to respond to an infection. We are now evaluating the distribution of WC1 gene expression among individual T cells to understand how subpopulations respond to specific pathogens. WC1 expressing γδ T cell clones were generated by infection with Theileria parva or by generation of long-lived memory cells to Leptospira Ag. To date, our findings suggest that the number of WC1 family members per an individual γδ T cell is restricted and stably expressed.
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Levy, Shoshana, et Yael Sagi. « Complementary Costimulation of Human T Cell Subpopulations by CD28 and CD81 ». Blood 118, no 21 (18 novembre 2011) : 1124. http://dx.doi.org/10.1182/blood.v118.21.1124.1124.
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Abstract Abstract 1124 CD81 is a widely expressed tetraspanin molecule that physically associates with CD4 and CD8 on the surface of human T cells. Coengagement of CD81 and CD3 results in the activation and proliferation of T cells. CD81 also costimulated mouse T cells that lack CD28, suggesting either a redundant or a different mechanism of action. Here we show that CD81 and CD28 have a preference for different subsets of T cells - primary human naïve T cells are better costimulated by CD81, while the memory T cell subsets and Tregs are better costimulated by CD28. The more efficient activation of naïve T cells by CD81 was due to prolonged signal transduction compared to that by CD28. We found that IL-6 played a role in the activation of the naïve T cell subset by CD81. Combined costimulation through both CD28 and CD81 resulted in an additive effect on T cell activation. Thus, these two costimulatory molecules complement each other both in the strength of signal transduction and in T cell subset inclusions. Costimulation via CD81 might be useful for expansion of T cells for adoptive immunotherapy to allow the inclusion of naïve T cells with their broad repertoire. Disclosures: No relevant conflicts of interest to declare.
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Kou, Zhong Chen, Joshua S. Puhr, Mabel Rojas, Wayne T. McCormack, Maureen M. Goodenow et John W. Sleasman. « T-Cell Receptor Vβ Repertoire CDR3 Length Diversity Differs within CD45RA and CD45RO T-Cell Subsets in Healthy and Human Immunodeficiency Virus-Infected Children ». Clinical Diagnostic Laboratory Immunology 7, no 6 (1 novembre 2000) : 953–59. http://dx.doi.org/10.1128/cdli.7.6.953-959.2000.
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ABSTRACT The T-cell receptor (TCR) CDR3 length heterogeneity is formed during recombination of individual Vβ gene families. We hypothesized that CDR3 length diversity could be used to assess the fundamental differences within the TCR repertoire of CD45RA and CD45RO T-cell subpopulations. By using PCR-based spectratyping, nested primers for all 24 human Vβ families were developed to amplify CDR3 lengths in immunomagnetically selected CD45RA and CD45RO subsets within both CD4+ and CD8+ T-cell populations. Umbilical cord blood mononuclear cells or peripheral blood mononuclear cells obtained from healthy newborns, infants, and children, as well as human immunodeficiency virus (HIV)-infected children, were analyzed. All T-cell subsets from newborn and healthy children demonstrated a Gaussian distribution of CDR3 lengths in separated T-cell subsets. In contrast, HIV-infected children had a high proportion of predominant CDR3 lengths within both CD45RA and CD45RO T-cell subpopulations, most commonly in CD8+ CD45RO T cells. Sharp differences in clonal dominance and size distributions were observed when cells were separated into CD45RA or CD45RO subpopulations. These differences were not apparent in unfractionated CD4+ or CD8+ T cells from HIV-infected subjects. Sequence analysis of predominant CDR3 lengths revealed oligoclonal expansion within individual Vβ families. Analysis of the CDR3 length diversity within CD45RA and CD45RO T cells provides a more accurate measure of disturbances in the TCR repertoire than analysis of unfractionated CD4 and CD8 T cells.
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Farace, F., F. Orlanducci, P. Y. Dietrich, C. Gaudin, E. Angevin, M. H. Courtier, C. Bayle, T. Hercend et F. Triebel. « T cell repertoire in patients with B chronic lymphocytic leukemia. Evidence for multiple in vivo T cell clonal expansions. » Journal of Immunology 153, no 9 (1 novembre 1994) : 4281–90. http://dx.doi.org/10.4049/jimmunol.153.9.4281.
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Abstract To characterize circulating T cell subpopulations in B chronic lymphocytic leukemia patients, TCR V alpha and V beta gene-segment use was analyzed by PCR using a panel of V gene-segment subfamily-specific oligonucleotide primers (V alpha 1-29/V beta 1-24). Virtually all V alpha and V beta subfamily specificities were expressed in these patients (nine stage A and four stage C), and the mean values obtained for each specificity were similar to those of a group of 13 healthy donors. Nonetheless, individual analysis revealed that unique V alpha or V beta gene-segment transcripts were overrepresented in patients compared with the control group. Overrepresentation of some TCR V beta chains was also detected by cytofluorometric analysis using a panel of 18 anti-V beta-specific mAbs. To further characterize these T cell subpopulations, we sequenced five different V beta-C beta PCR products in two selected stage A patients and found highly predominant recurrent transcripts in each of the five V beta specificities (50% to 100% of the analyzed sequences with identical V(D)J regions). These results were confirmed on bulk cDNA (i.e., without cloning) and extended to other V beta specificities (up to nine clonal expansions of 24 V beta specificities in one patient) and two other patients using a PCR-based method that determines V(D)J junction size patterns. Finally, it was observed that a V beta 19+ T cell subpopulation was clonally expanded in one patient to up to 30% of circulating T cells. This V beta 19+ CD8+ T cell clone was shown to specifically recognize the autologous tumor cells in vitro, as determined in cytokine release assays. Together, these results support the view that multiple expansions of unique T cell clones may derive in vivo from B chronic lymphocytic leukemia tumor-associated Ag stimulation.