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1
Hyc, Anna, Jacek Malejczyk, Anna Osiecka, and Stanislaw Moskalewski. "Immunological Response against Allogeneic Chondrocytes Transplanted into Joint Surface Defects in Rats." Cell Transplantation 6, no. 2 (March 1997): 119–24. http://dx.doi.org/10.1177/096368979700600205.
Повний текст джерелаАнотація:
Rat chondrocytes isolated from the articular–epiphyseal cartilage complex were transplanted into defects prepared in articular cartilage and subchondral bone. Transplants were taken for examination after 3 and 8 wk. Cartilage formed by syngeneic chondrocytes did not evoke formation of infiltrations. Contrary to that, in the vicinity of cartilage produced by allogeneic chondrocytes numerous infiltrating cells were present and cartilage resorption could be observed. Cyclosporine-A (CsA) treatment of recipients of allogeneic chondrocytes only partially suppressed accumulation of infiltrating cells and matrix resorption. Antichondrocyte immune response of chondrocyte graft recipients was studied by evaluation of spleen mononuclear cells (SMC) stimulation in mixed splenocytechondrocyte cultures and by evaluation of antichondrocyte cytotoxic antibodies. No difference in stimulation of SMC from intact rats by syngeneic and allogeneic chondrocytes was observed. Stimulation by allogeneic chondrocytes was slightly but significantly higher in recipients of syngeneic grafts. SMC of allogenic chondrocyte recipients were strongly stimulated by allogeneic chondrocytes. This response was absent in recipients treated with CsA. Spontaneous antichondrocyte cytotoxic antibody activity was detected in intact rats and in recipients of syngeneic grafts. In recipients of allogeneic chondrocytes the antibody response against allogeneic chondrocytes was raised but was statistically not significant owing to the considerable variation in the level of spontaneously occurring antichondrocyte antibodies.
2
Martínez-Varea, Alicia, Begoña Pellicer, Alfredo Perales-Marín, and Antonio Pellicer. "Relationship between Maternal Immunological Response during Pregnancy and Onset of Preeclampsia." Journal of Immunology Research 2014 (2014): 1–15. http://dx.doi.org/10.1155/2014/210241.
Повний текст джерелаАнотація:
Maternofetal immune tolerance is essential to maintain pregnancy. The maternal immunological tolerance to the semiallogeneic fetus becomes greater in egg donation pregnancies with unrelated donors as the complete fetal genome is allogeneic to the mother. Instead of being rejected, the allogeneic fetus is tolerated by the pregnant woman in egg donation pregnancies. It has been reported that maternal morbidity during egg donation pregnancies is higher as compared with spontaneous orin vitrofertilization pregnancies. Particularly, egg donation pregnancies are associated with a higher incidence of pregnancy-induced hypertension and placental pathology. Preeclampsia, a pregnancy-specific disease characterized by the development of both hypertension and proteinuria, remains the leading cause of maternal and perinatal mortality and morbidity. The aim of this review is to characterize and relate the maternofetal immunological tolerance phenomenon during pregnancies with a semiallogenic fetus, which are the spontaneously conceived pregnancies andin vitrofertilization pregnancies, and those with an allogeneic fetus or egg donation pregnancies. Maternofetal immune tolerance in uncomplicated pregnancies and pathological pregnancies, such as those with preeclampsia, has also been assessed. Moreover, whether an inadequate maternal immunological response to the allogenic fetus could lead to a higher prevalence of preeclampsia in egg donation pregnancies has been addressed.
3
Fabre, John W. "The allogeneic response and tumor immunity." Nature Medicine 7, no. 6 (June 2001): 649–52. http://dx.doi.org/10.1038/89008.
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4
Jones, RJ, RF Ambinder, S. Piantadosi, and GW Santos. "Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation." Blood 77, no. 3 (February 1, 1991): 649–53. http://dx.doi.org/10.1182/blood.v77.3.649.649.
Повний текст джерелаАнотація:
Abstract The existence of an immunologic antileukemia reaction associated with allogeneic bone marrow transplantation (BMT) is well established. However, a similar graft-versus-tumor effect against lymphomas has not been demonstrated. We analyzed the results of BMT in 118 consecutive patients with relapsed Hodgkin's disease or aggressive non-Hodgkin's lymphoma. The 38 patients less than 50 years of age with HLA-matched donors had allogenic marrow transplants, and the other 80 patients received purged autologous grafts. The median age was 26 years in both the allogeneic and the autologous graft recipients. The patient's response to conventional salvage therapy before transplant was the only factor that influenced the event-free survival after BMT (P less than .001). Both the patient's response to salvage therapy before BMT (P less than .001) and the type of graft (P = .02) significantly influenced the probability of relapse after BMT. The actuarial probability of relapse in patients who responded to conventional salvage therapy before BMT was only 18% after allogenic BMT compared with 46% after autologous BMT. However, the actuarial probability of event-free survival at 4 years was the same, 47% versus 41%, for patients with responsive lymphomas who received allogeneic and autologous transplants, respectively (P = .8). The beneficial antitumor effect of allogeneic BMT was offset by its higher transplant-related mortality (P = .01), largely resulting from graft-versus-host disease. Allogeneic BMT appears to induce a clinically significant graft-versus- lymphoma effect. The magnitude of this effect is similar to that reported against leukemias.
5
Jones, RJ, RF Ambinder, S. Piantadosi, and GW Santos. "Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation." Blood 77, no. 3 (February 1, 1991): 649–53. http://dx.doi.org/10.1182/blood.v77.3.649.bloodjournal773649.
Повний текст джерелаАнотація:
The existence of an immunologic antileukemia reaction associated with allogeneic bone marrow transplantation (BMT) is well established. However, a similar graft-versus-tumor effect against lymphomas has not been demonstrated. We analyzed the results of BMT in 118 consecutive patients with relapsed Hodgkin's disease or aggressive non-Hodgkin's lymphoma. The 38 patients less than 50 years of age with HLA-matched donors had allogenic marrow transplants, and the other 80 patients received purged autologous grafts. The median age was 26 years in both the allogeneic and the autologous graft recipients. The patient's response to conventional salvage therapy before transplant was the only factor that influenced the event-free survival after BMT (P less than .001). Both the patient's response to salvage therapy before BMT (P less than .001) and the type of graft (P = .02) significantly influenced the probability of relapse after BMT. The actuarial probability of relapse in patients who responded to conventional salvage therapy before BMT was only 18% after allogenic BMT compared with 46% after autologous BMT. However, the actuarial probability of event-free survival at 4 years was the same, 47% versus 41%, for patients with responsive lymphomas who received allogeneic and autologous transplants, respectively (P = .8). The beneficial antitumor effect of allogeneic BMT was offset by its higher transplant-related mortality (P = .01), largely resulting from graft-versus-host disease. Allogeneic BMT appears to induce a clinically significant graft-versus- lymphoma effect. The magnitude of this effect is similar to that reported against leukemias.
6
Wu, Yongxia, Corey Mealer, Mohammed Sofi, Linlu Tian, David Bastian, Steven Schutt, Hee-Jin Choi, Chih-Hang Anthony Tang, Chih-Chi Andrew Hu, and Xue-Zhong Yu. "STING Negatively Regulates Allogeneic T Cell Responses by Constraining Function of Antigen Presenting Cells." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 87.11. http://dx.doi.org/10.4049/jimmunol.204.supp.87.11.
Повний текст джерелаАнотація:
Abstract Stimulator of interferon genes (STING) plays an important role in eliciting innate immune responses by sensing tumor and microbial DNA in anti-tumor and anti-infection responses, respectively. How the STING signal affects allogeneic response is not clear. To address this question, we utilized murine models of allogeneic hematopoietic stem cell transplantation (allo-HCT). By transferring donor bone marrow (BM) and T cells into allogeneic recipients, we found that significantly more severe graft-versus-host disease (GVHD) was induced in STING−/− recipients as compared to WT controls. By generating BM-chimeric mice in which STING was deficient in hematopoietic or non-hematopoietic antigen-presenting cells (APCs), we confirmed that STING on hematopoietic cells was primarily responsible for constraining host APC function. We further demonstrated that STING on host CD11c+ APCs played a predominant role in the regulation of allogenic T-cell responses. Mechanistically, we found that host CD11c+IAb+ cells deficient for STING could survive better and be activated more strongly after allo-HCT. As a consequence, STING-deficient APCs augmented donor T-cell expansion, chemokine receptor expression and migration into intestinal tissues, resulting accelerated/exacerbated GVHD after allo-HCT. Using pharmacologic approaches, we further demonstrated that systemic administration of STING agonist (c-diGMP) on recipient mice before irradiation significantly reduced GVHD mortality. In conclusion, we reveal a novel role of STING in APC activity that dictates T-cell allogenic responses, and validate STING as a potential therapeutic target for controlling GVHD after allo-HCT.
7
Fedoseyeva, Eugenia V., Feng Zhang, Patricia L. Orr, David Levin, Harry J. Buncke, and Gilles Benichou. "De Novo Autoimmunity to Cardiac Myosin After Heart Transplantation and Its Contribution to the Rejection Process." Journal of Immunology 162, no. 11 (June 1, 1999): 6836–42. http://dx.doi.org/10.4049/jimmunol.162.11.6836.
Повний текст джерелаАнотація:
Abstract Allograft rejection is initiated by an immune response to donor MHC proteins. We recently reported that this response can result in breakdown of immune tolerance to a recipient self Ag. However, the contribution of this autoimmune response to graft rejection has yet to be determined. Here, we found that after mouse allogeneic heart transplantation, de novo CD4+ T cell and B cell autoimmune response to cardiac myosin (CM), a major contractile protein of cardiac muscle, is elicited in recipients. Importantly, CM is the autoantigen that causes autoimmune myocarditis, a heart autoimmune disease whose histopathological features resemble those observed in rejected cardiac transplants. Furthermore, T cell responses directed to CM peptide myhcα 334–352, a known myocarditogenic determinant, were detected in heart-transplanted mice. No responses to CM were observed in mice that had received an allogeneic skin graft or a syngeneic heart transplant, demonstrating that this response is tissue specific and that allogeneic response is necessary to break tolerance to CM. Next, we showed that sensitization of recipient mice with CM markedly accelerates the rejection of allogeneic heart. Therefore, posttransplant autoimmune response to CM is relevant to the rejection process. We conclude that transplantation-induced autoimmune response to CM represents a new mechanism that may play a significant role in cardiac transplant rejection.
8
Lakkis, F. G., and R. I. Lechler. "Origin and Biology of the Allogeneic Response." Cold Spring Harbor Perspectives in Medicine 3, no. 8 (August 1, 2013): a014993. http://dx.doi.org/10.1101/cshperspect.a014993.
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9
Bumgardner, G. L., J. Li, M. B. Heininger, D. Xia, J. Parker-Thornberg, C. G. Orosz, and R. M. Ferguson. "In vivo immune response to allogeneic hepatocytes." Transplantation Proceedings 29, no. 4 (June 1997): 2059–60. http://dx.doi.org/10.1016/s0041-1345(97)00230-3.
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10
Riteau, Beatrice, Catherine Menier, Iman Khalil-Daher, Christine Sedlik, Jean Dausset, Nathalie Rouas-Freiss, and Edgardo D. Carosella. "HLA-G inhibits the allogeneic proliferative response." Journal of Reproductive Immunology 43, no. 2 (July 1999): 203–11. http://dx.doi.org/10.1016/s0165-0378(99)00034-0.
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11
Hiramoto, Raymond N., Chi-Mei Hsueh, Carolyn F. Rogers, Sossiena Demissie, Nancy S. Hiramoto, Seng-Jaw Soong, and Vithal K. Ghanta. "Conditioning of the allogeneic cytotoxic lymphocyte response." Pharmacology Biochemistry and Behavior 44, no. 2 (February 1993): 275–80. http://dx.doi.org/10.1016/0091-3057(93)90462-3.
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12
Reinsmoen, N. L., and F. H. Bach. "2.2-06 Indirect response to allogeneic peptides." Human Immunology 26 (January 1989): 11. http://dx.doi.org/10.1016/0198-8859(89)90613-7.
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13
Pardoux, C., C. Asselin-Paturel, J. Chehimi, F. Gay, F. Mami-Chouaib, and S. Chouaib. "Functional interaction between TGF-beta and IL-12 in human primary allogeneic cytotoxicity and proliferative response." Journal of Immunology 158, no. 1 (January 1, 1997): 136–43. http://dx.doi.org/10.4049/jimmunol.158.1.136.
Повний текст джерелаАнотація:
Abstract IL-12 is an important cytokine in the control of cell-mediated immunity. We have investigated the functional interaction of IL-12 with TGF-beta1, a cytokine involved in the regulation of growth and differentiation of immunocompetent cells, during human allogeneic response development. Using primary MLR, our data show that addition of exogenous TGF-beta at the sensitizing phase of the primary MLR resulted in the inhibition of both allogeneic cytotoxic and proliferative responses. The inhibitory effect of TGF-beta on allogeneic response involves an abrogation of IL-12/p70 production upon allostimulation. In contrast to its effect on IL-12 production, TGF-beta did not alter the expression of IL-12R beta1-chain (IL-12R beta) in T cells induced upon allogeneic activation. Addition of exogenous IL-12 or IFN-gamma in the MLR cultures in the presence of TGF-beta did not result in reversal of CTL generation and T cell proliferation. Interestingly, TGF-beta was efficient in down-regulating IL-12 responsiveness of alloactivated T cells as well as TCR-alphabeta or TCR-gammadelta alloreactive T cell clones. These studies suggest that the inhibitory effect of TGF-beta on the development of human allogeneic proliferation and cytotoxic responses involves an additional mechanism associated with an interference with IL-12 pathway.
14
Williams, R. Michael. "Antigen altered idiotype induces immune regulation implications for cancer, autoimmunity and AIDS (61.17)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 61.17. http://dx.doi.org/10.4049/jimmunol.186.supp.61.17.
Повний текст джерелаАнотація:
Abstract Antigen altered idiotype regulates specific immune responses. Mendelian segregation of a given +/- phenotype defines an immune response gene (IR-X) . Autoimmunity producing anti-self clones must be eliminated or specifically suppressed, so a large portion of the antigenic repertoire resembles allogeneic MHC molecules. Singer and Williams (Cell Immunol.1978: 4:1) proposed that exposure to many allogeneic HLA molecules could eventually overlap with important responses to pathogens, causing serious holes in the repertoire, some large enough to produce an acquired immunodeficiency syndrome (AIDS). The changes resulting from exposure to multiple incompatible allogeneic MHC molecules could also produce the opposite effect, an increase in a desirable immune response, or the allogeneic effect . IR-genes for histocompatible tumor resistance localized to the mouse MHC (Cancer Res. 1975;35:1586) The patient with HIV and AML, who was rendered free of both by transplantation of the right allogeneic stem cells (Blood,2010,Dec 8) supports our case. We propose that HIV is a unique and potent inducer of altered idiotype immune suppression. Explanation of the mechanism for synthetic antigens by Benacerraf (Nobel, 1980) and for viruses by Zinkernagel and Doherty (Nobel, 1986) followed from the idiotype network concept of Jerne (Nobel, 1984). Our attempt to relate these observations to the MHC and genetically controlled immune responses led us to the altered idiotype hypothesis.
15
Fujisawa, Kenji, Shinya Saito, Yutaka Okada, Toshiyosi Fujiwara, Takahito Yagi, Hiromi Iwagaki, and Noriaki Tanaka. "Suppression of Allogeneic Response by Viral IL-10 Gene Transfer." Cell Transplantation 12, no. 4 (May 2003): 379–87. http://dx.doi.org/10.3727/000000003108746920.
Повний текст джерелаАнотація:
Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines, such as IL-10, have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic rats (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, vIL-10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high vIL-10 level in the splenic vein in NAR transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent allogeneic response in hepatocyte transplantation.
16
Krackhardt, Angela M., Sabine Harig, Mathias Witzens, Ryan Broderick, Patrick Barrett, and John G. Gribben. "T-cell responses against chronic lymphocytic leukemia cells: implications for immunotherapy." Blood 100, no. 1 (July 1, 2002): 167–73. http://dx.doi.org/10.1182/blood.v100.1.167.
Повний текст джерелаАнотація:
Abstract Chronic lymphocytic leukemia (CLL) cells are ineffective antigen-presenting cells (APCs) although CD40-activated CLL cells can stimulate proliferation of autologous and allogeneic T cells. We examined the antigen-presenting capacity of CD40-activated CLL cells as well as dendritic cells pulsed with apoptotic bodies of CLL cells to generate autologous and allogeneic immune responses against CLL cells. Both APC types were capable of generating T-cell lines that proliferate specifically in response to unstimulated CLL cells. Whereas cytotoxic responses against stimulated and unstimulated CLL cells could be repeatedly generated by allogeneic healthy donors, autologous cytotoxic immune responses against CD40-activated and native CLL cells were rarely detected. However, T cells isolated from patients with CLL could recognize and lyse allogeneic stimulated and unstimulated CLL cells, demonstrating that cytotoxic T cells from these tumor-bearing patients are functionally intact.
17
Irie, Atsushi, and Yasuharu Nishimura. "Basic immunology of immune response to allogeneic HLA." Major Histocompatibility Complex 20, no. 2 (2013): 109–20. http://dx.doi.org/10.12667/mhc.20.109.
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18
Peñuelas-Rivas, G., R. Domínguez-Perles, V. Brinkmann, M. L. del Rio, A. Muñoz-Luna, P. Ramírez-Romero, P. Parrilla-Paricio, and J. I. Rodríguez-Barbosa. "FTY720 Inhibits TH1-Mediated Allogeneic Humoral Immune Response." Transplantation Proceedings 37, no. 9 (November 2005): 4124–26. http://dx.doi.org/10.1016/j.transproceed.2005.09.184.
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19
ONeill, Rachel, Nicholas Leigh, Wei Du, Sandeep Kumar, Chuan Chen, Jingxin Qiu, George Chen, et al. "CD27/CD70 mediated negative regulation of inflammatory T cell response." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 140.11. http://dx.doi.org/10.4049/jimmunol.196.supp.140.11.
Повний текст джерелаАнотація:
Abstract Costimulatory pathways are involved in T cell activation and function. The costimulatory molecule CD27 is a TNF receptor family member expressed on T cells and its ligand, CD70, is known to be expressed on activated antigen-presenting cells, T-, B- and NK cells. The CD27/CD70 pathway has been shown to be critical for T cell activation, differentiation and survival. In this study we have used murine models to study the roles of CD27/CD70 in allogeneic graft-versus-host disease (GVHD) and syngeneic inflammatory bowel disease (IBD). Our results reveal a novel and negative regulatory role played by this pathway as specified in 3 aspects: 1) Allogeneic hematopoietic cell transplantation (allo-HCT) shows that both CD27−/− and CD70−/− donor T cells caused more severe GVHD than WT donor T cells, suggesting that CD27/CD70 signaling in donor T cells inhibits allogeneic T cell response. 2) When transplanted into syngeneic RAG1−/− hosts in an autoimmune IBD model, both CD27−/− and CD70−/− donor CD4+ CD25− T cells caused more severe IBD than WT T cells, suggesting that CD27/CD70 signaling in T cells inhibits autoimmune T cell response. 3) When used as hosts for allo-HCT, both CD27−/− and CD70−/− mice exhibited more severe GVHD compared to WT mice, suggesting that CD27/CD70 signaling in the host inhibits allogeneic T cell response. Mechanistic analyses reveal that this pathway executes immune suppression by limiting T cell expansion and effector function (e.g., TNFa and IFNg production) via a regulatory T cell-independent mechanism that at least partially involves activation-induced T cell death. Overall, our study demonstrates that CD27/CD70 signaling plays a novel role in suppressing allogeneic and autoimmune inflammatory T cell responses.
20
Pao, Mary, Esperanza B. Papadopoulos, Farid Boulad, Hugo Castro-Malaspina, Ann Jakubowski, Nancy A. Kernan, Miguel Perales, et al. "Response to Immunizations Following Allogeneic HCT with Adjuvant Rituximab Therapy." Blood 106, no. 11 (November 16, 2005): 3242. http://dx.doi.org/10.1182/blood.v106.11.3242.3242.
Повний текст джерелаАнотація:
Abstract Use of anti-CD20 monoclonal antibody after allogeneic HCT for the treatment EBV lymphoma or viremia, autoimmune cytopenias, and the prevention or treatment of recurrent NHL has become more frequent. There is limited data on the effect of this therapy on specific antibody production following allogeneic HCT. We therefore examined the response to standard childhood immunizations of 30 patients, including 20 adults (>18 years of age) who received rituximab following a T cell depleted (n=26) or unmodified (n=4) HCT at our institution. T cell function was assessed in vitro by proliferative response to PHA and B cell reconstitution was confirmed by recovery of CD19+ and CD20+ circulating lymphocytes. Patients received a median (range) of 4 (1–12) doses of rituximab, with 15 patients receiving 4–6 doses. The median age of the patient population was 28.5 years with a range of 0.8–63.0 years. Children (median age: 8.5 yrs) received a transplant from an unrelated (n=7), HLA mismatched related (n=2), or HLA matched related (n=1) donor and adults (median age: 42.5 yrs), received a transplant from an unrelated (n=7), HLA mismatched related (n=2), or HLA-matched related (n=11) donor. Patients were vaccinated when their PHA response was at least 75% of the lower limit of normal and CD20+ cells were >100/ul. Vaccination was initiated at a median of 270 and 525 days following the last dose of rituximab in children and adults, respectively. A two to 3-fold rise in titers following a series of 3 tetanus and IPV vaccinations occurred in 19 of 21 and 19 of 19 evaluable patients, respectively. Although 8 of 9 children responded to the H flu conjugate vaccine, only 5 of 13 adults mounted an adequate response. Eighteen patients received the recombinant Hepatitis B vaccine. Nine responded following the initial series (5/7 children, 4/11 adults). Two of three patients who failed initial Hepatitis B vaccination, responded to a second series (1 child, 1 adult). Response to pneumococcal vaccination was the least consistent. None of 11 adults who received the unconjugated 23-valent pneumococcal vaccine developed an adequate response. In view of this observation, children given rituximab were immunized with the conjugated pneumococcal vaccine. Four of eight children responded to the initial series, and two additional children responded following a second series. These preliminary data suggest that both adult and pediatric patients given rituximab following an allogeneic HCT can mount successful antibody responses to standard T-helper cell dependent vaccines. However, B cell responses to T cell independent vaccines may be particularly impaired. Larger prospective trials, stratified by age, comparing vaccine responses in patients following allogeneic transplant in the presence or absence of post transplant rituximab therapy are warranted.
21
Brás, Gil, Carlos Vaz, Luís Leite, Rosa Branca, Fernando Campilho, Susana Roncón, and Antonio M. Campos. "Reduced-Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma in Relapse after Autologous Transplantation: A Single Institution Experience with Matched Related Donors." Blood 128, no. 22 (December 2, 2016): 5873. http://dx.doi.org/10.1182/blood.v128.22.5873.5873.
Повний текст джерелаАнотація:
Abstract INTRODUCTION: Relapse in Multiple Myeloma (MM) comprises a dismal prognosis. The proteasome inhibitors and immunomodulators increased the median overall survival (OS) in relapse from 12 to 24 months. For relapsing patients, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) and also allogeneic HSCT have been considered valid options in recent consensus statement. The major concern about allogeneic HSCT is the high transplant-related mortality (TRM) even with Reduced Intensity Conditioning (RIC). AIMS: Single institution retrospective evaluation of RIC allogeneic HSCT from matched related donors, in a cohort of MM patients relapsing after autologous HSCT. RESULTS: Between 1998 and 2016, 43 MM patients received allogeneic HSCT. From this group, a cohort of 29 MM patients relapsing after autologous HSCT was selected, based on supracited inclusion criteria. The median age at allogeneic HSCT was 51 (33-62) years. Before allogeneic HSCT, 55,7% (N=16) were treated wih salvage chemotherapy alone, whereas 20,7% (N=6) received chemotherapy plus autologous HSCT. For allogeneic HSCT, the conditioning was fludarabine plus bussulphan. Acute graft-versus-host disease (GVHD) prophylaxis was cyclosporine plus mycophenolate mophetil in 25 (86,2%) and in vivo antithymocyte globulin plus cyclosporine in 4 (13,8%). All patients recieved matched related peripheral blood grafts. Responses to salvage treatment previous to allogeneic HSCT were: progressive/stable disease (PD/SD) 24,1%, partial response (PR) 41,4%, very good partial response/complete remission (VGPR/CR) 13,7%, unknown 20,7%. Best responses after allogeneic HSCT were: PD/SD 15,7%, PR 24,1%, VGPR/CR 58,6%, unknown 10,3%. Engraftment was achived in 86,2% (N=25) and full donor chimerism was observed, at least once, in 72,4% (N=21). The overall reported incidence of grade II-IV acute GVHD was 48,3% (N=14) and moderate/severe chronic GVHD was 34,5% (N=10). Cytomegalovirus (CMV) reactivation ocurred in 44,8% (N=13) and hemorrhagic cystitis in 10,3% (N=3). The median progression free survival (PFS) and overall survival (OS) was 24 (0-61) and 176 (0-376) months, respectively. The incidence of relapse/progression was 48% (N=14). In this setting, 42,9% (N=6) were treated with chemotherapy alone and 35,7% (N=5) with donor lymphocyte infusion (DLI). After DLI, 80% (N=4) achieved CR. The overall mortality and TRM were 48,3% (N=14) and 17,2% (N=5), respectively. Best response after allogeneic HSCT was the only factor that improved PFS and OS (p<0,05). CONCLUSION: In our cohort, the allogeneic HSCT as salvage treatment for MM relapsing after autologous HSCT showed ability to deepen responses after salvage chemotherapy/autologous HSCT and also to prolong OS. The diferences between PFS and OS probably reflect the increasing therapeutical options to rescue patients after progression/relapse (chemotherapy, immunossupression tapper and DLI). The scarce data concerning the cytogenetic risk and the short dimension of this cohort are major limitations to define the MM relapsing patients who benefit most of allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.
22
Down, JD, NJ Tarbell, HD Thames, and PM Mauch. "Syngeneic and allogeneic bone marrow engraftment after total body irradiation: dependence on dose, dose rate, and fractionation." Blood 77, no. 3 (February 1, 1991): 661–69. http://dx.doi.org/10.1182/blood.v77.3.661.661.
Повний текст джерелаАнотація:
Abstract Murine bone marrow chimera models were used to assess the efficacy of host total body irradiation (TBI) given at different doses, dose rates, and fractionation schemes in providing for engraftment of syngeneic and allogeneic bone marrow. B6-Hbbd congenic and LP mice, respectively, were used as donors (10(7) bone marrow cells) for syngeneic and allogenic (H-2 compatible) transplantation in standard B6 recipients. Stable marrow chimerism was determined from host and donor stem cell- derived hemoglobin phenotypes (Hbbs and Hbbd) on gel electrophoresis at 3 months posttransplant. Partial engraftment of syngeneic marrow was seen at single doses as low as 2 Gy, with the donor component increasing steadily with increasing TBI dose to a level of 100% at 7 Gy. Immunologic resistance of the host appeared to prevent allogeneic engraftment until 5.5 Gy. A very steep radiation dose response was then observed so that the level of chimerism with 6 Gy and above became comparable with syngeneic engraftment. Low dose rate (5 cGy minute-1) and fractionated TBI required higher total doses for equivalent engraftment (radiation dose-sparing) in both syngeneic and allogenic bone marrow transplantation. This displacement in the dose-response curve on fractionation was seen with interfraction intervals of 3 and 6 hours. A further dose-sparing effect was observed on extending the interval to 18 and 24 hours, but only for allogeneic transplantation, and may therefore be related to recovery of immune-mediated graft resistance. The involvement of multiple target cell populations in determining allogenic engraftment rendered the application of the linear-quadratic model for radiation cell survival problematic in this case. The recovery in dose when low dose rate and 6-hour interfraction intervals were applied in either syngeneic or allogeneic BMT is consistent with appreciable sub-lethal damage repair in the primitive self-renewing stem cell population of the host marrow. These results contrast with the poor repair capacity of the 11-day spleen colony- forming units (CFUs) population after fractionated irradiation and support the notion that ablation of early stem cells in the pre-CFUs compartment is essential for long-term marrow engraftment.
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Down, JD, NJ Tarbell, HD Thames, and PM Mauch. "Syngeneic and allogeneic bone marrow engraftment after total body irradiation: dependence on dose, dose rate, and fractionation." Blood 77, no. 3 (February 1, 1991): 661–69. http://dx.doi.org/10.1182/blood.v77.3.661.bloodjournal773661.
Повний текст джерелаАнотація:
Murine bone marrow chimera models were used to assess the efficacy of host total body irradiation (TBI) given at different doses, dose rates, and fractionation schemes in providing for engraftment of syngeneic and allogeneic bone marrow. B6-Hbbd congenic and LP mice, respectively, were used as donors (10(7) bone marrow cells) for syngeneic and allogenic (H-2 compatible) transplantation in standard B6 recipients. Stable marrow chimerism was determined from host and donor stem cell- derived hemoglobin phenotypes (Hbbs and Hbbd) on gel electrophoresis at 3 months posttransplant. Partial engraftment of syngeneic marrow was seen at single doses as low as 2 Gy, with the donor component increasing steadily with increasing TBI dose to a level of 100% at 7 Gy. Immunologic resistance of the host appeared to prevent allogeneic engraftment until 5.5 Gy. A very steep radiation dose response was then observed so that the level of chimerism with 6 Gy and above became comparable with syngeneic engraftment. Low dose rate (5 cGy minute-1) and fractionated TBI required higher total doses for equivalent engraftment (radiation dose-sparing) in both syngeneic and allogenic bone marrow transplantation. This displacement in the dose-response curve on fractionation was seen with interfraction intervals of 3 and 6 hours. A further dose-sparing effect was observed on extending the interval to 18 and 24 hours, but only for allogeneic transplantation, and may therefore be related to recovery of immune-mediated graft resistance. The involvement of multiple target cell populations in determining allogenic engraftment rendered the application of the linear-quadratic model for radiation cell survival problematic in this case. The recovery in dose when low dose rate and 6-hour interfraction intervals were applied in either syngeneic or allogeneic BMT is consistent with appreciable sub-lethal damage repair in the primitive self-renewing stem cell population of the host marrow. These results contrast with the poor repair capacity of the 11-day spleen colony- forming units (CFUs) population after fractionated irradiation and support the notion that ablation of early stem cells in the pre-CFUs compartment is essential for long-term marrow engraftment.
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Jones, M. C., D. A. Power, K. N. Stewart, and G. R. D. Catto. "Cyclosporin a prevents sensitization after blood transfusion in multiparous rats." Clinical Science 74, no. 4 (April 1, 1988): 389–92. http://dx.doi.org/10.1042/cs0740389.
Повний текст джерелаАнотація:
1. Humoral immune responses to allogeneic blood transfusions and semi-allogeneic pregnancies were monitored by the indirect haemagglutination assay in strains of inbred rats. 2. Similar titres and ranges of cross-reactive allo-antibodies were induced by blood transfusions and pregnancy; the maternal alloantibody response to paternal antigens was not increased by an unrelated antigenic stimulus. 3. Immunosuppression with cyclosporin, A was effective in preventing the primary humoral immune response produced by blood transfusion but not in abrogating the established immune response to previous pregnancy. 4. These studies have established an animal model of sensitization that both stimulates, the clinical situation of many potential renal transplant recipients and permits analyses of the different antigenic stimuli involved.
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Chu, Cheng-Feng, Shih-Hsuan Mao, Victor Bong-Hang Shyu, Chih-Hao Chen, and Chien-Tzung Chen. "Allogeneic Bone-Marrow Mesenchymal Stem Cell with Moldable Cryogel for Craniofacial Bone Regeneration." Journal of Personalized Medicine 11, no. 12 (December 7, 2021): 1326. http://dx.doi.org/10.3390/jpm11121326.
Повний текст джерелаАнотація:
Allogeneic bone-marrow mesenchymal stem cells (BMSCs) can promote bone regeneration and substitute for autologous BMSCs if autologous sources are unavailable, but the efficacy of bone regeneration by allogeneic BMSCs is still inconsistent. A Lewis rat cranium defect model was used to investigate the efficacy of bone regeneration between autologous and allogeneic BMSCs in gelatin-nanohydroxyapatite cryogel scaffolds. BMSCs from Wistar rats served as the allogeneic cell lineage. The full-thickness cranium defects were treated by either blank control, cryogel only, allogeneic BMSC-seeded cryogel, or autologous BMSC-seeded cryogel (n = 5). Bone regeneration was monitored by micro-computed tomography and examined histologically at week 12. In addition, we assessed the immune responses in vitro by mixed lymphocyte reaction (MLR) assay and CD4+ immunochemistry staining ex vivo. The MLR showed that allogeneic BSMCs elicited a weak immune response on day 14 that progressively attenuated by day 28. In vivo, the bone regeneration in allogeneic BMSCs was inferior at week 4, but progressively matched the autologous BMSCs by week 12. Our results suggest that allogeneic BMSCs can serve as an alternative source for bone regeneration.
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Jackman, Rachael, Marcus Muench, John Heitman, Heather Inglis, Jacqueline Law, Susanne Marschner, Raymond Goodrich, and Philip Norris. "Immune modulation and prevention of alloimmunization following transfusion with pathogen reduced platelets (P2144)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 69.10. http://dx.doi.org/10.4049/jimmunol.190.supp.69.10.
Повний текст джерелаАнотація:
Abstract Blood transfusion is the most commonly performed allogeneic transplant, and results in alloimmunization of a number of recipients, potentially complicating subsequent transfusions as well as solid organ transplants. The use of a pathogen reduction method using riboflavin and UV light has been shown to induce changes in WBCs that result in a failure to stimulate allogeneic PBMCs in vitro. We assessed the degree of alloimmunization in vivo using mice given pathogen reduced versus untreated allogeneic platelets. WBC-enriched platelet rich plasma (PRP) was prepared from C57Bl/6 and Balb/cJ donor mice and either left untreated or pathogen reduced before transfusion via tail vein into Balb/cJ mice. Two weeks after transfusion circulating alloantibodies were measured, as were splenocyte cytokine responses to challenge with donor type cells ex vivo. Pathogen reduction treatment of allogeneic PRP prior to transfusion blocked alloimmunization. Mice that were transfused with untreated PRP following previous transfusion with pathogen reduced PRP had a normal alloantibody response, but their splenic lymphocytes had a reduced cytokine response to allogeneic challenge ex vivo. This immune modulation required the presence of WBCs in the transfused PRP and was donor specific. These results imply that UV treatment of blood products has the potential to modulate subsequent exposure to alloantigens, with implications for tolerance and organ transplantation.
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Oliveira, Régis Linhares, Pedro Cesar Chagastelles, Patrícia Sesterheim, and Patricia Pranke. "In Vivo Immunogenic Response to Allogeneic Mesenchymal Stem Cells and the Role of Preactivated Mesenchymal Stem Cells Cotransplanted with Allogeneic Islets." Stem Cells International 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/9824698.
Повний текст джерелаАнотація:
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into cells from the mesenchymal lineage. The hypoimmunogenic characteristic of MSCs has encouraged studies using allogeneic MSCs for the treatment of autoimmune diseases and inflammatory conditions. Promising preclinical results and the safety of allogeneic MSC transplantation have created the possibility of “off-the-shelf” clinical application of allogeneic cells. This study has aimed to evaluate the survival of untreated and IFN-γ- and TNF-α-treated (preactivated) allogeneic MSCs transplanted under the kidney capsule of immunocompetent mice together with the role of preactivated MSCs after cotransplantation with allogeneic islets. The preactivation of MSCs upregulated the gene expression of anti-inflammatory molecules and also enhanced their immunomodulatory capacity in vitro. In vivo, allogeneic MSCs provoked an immunogenic response, with the infiltration of inflammatory cells at the transplant site and full graft rejection in both the untreated and preactivated groups. Allogeneic islets cotransplanted with preactivated MSCs prolonged graft survival for about 6 days, compared with islet alone. The present results corroborate the hypothesis that allogeneic MSCs are not immune-privileged and that after playing their therapeutic role they are rejected. Strategies that reduce allogeneic MSC immunogenicity can potentially prolong their in vivo persistence and improve the therapeutic effects.
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Sato, Hideaki, Ayumi Wakayama, Kyoko Ito, Ikuo Kashiwakura, and Koichi Ito. "Functional Adaptive Immune Responses in Hematopoietic Chimeric Mice After Umbilical Cord Blood Cell Transplantation." Blood 120, no. 21 (November 16, 2012): 2995. http://dx.doi.org/10.1182/blood.v120.21.2995.2995.
Повний текст джерелаАнотація:
Abstract Abstract 2995 Introduction: An increasing number of clinical trials have demonstrated the usefulness of cord blood as a source of hematopoietic stem cells for reconstitution of the hematopoietic system. Nevertheless, due to a lack of convenient animal models, information about the immunological competence of umbilical cord blood cell (UCBC)-derived lymphocytes has been relatively limited. Recently, we have established a murine model of UCBC transplantation, which reconstitutes the hematopoietic system of immunodeficient mice, and studied the correct immunological functions of UCBC-derived lymphocytes generated in an allogeneic environment. Materials and Methods: UCBC prepared from C57BL/6 (H-2b) mice were transferred into lethally irradiated BALB/c (H-2d) mice lacking T- and B-lymphocytes (RAG2 knockout). In order to evaluate the adaptive immune response in the recipient mice, rejection of skin grafts from third-party C3H/He (H-2k) mice and antibody responses to immunization with a T-dependent antigen, 2,4,6-trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH), were assessed. Additionally, the responsiveness of generated T cells was verified by mixed lymphocyte reaction (MLR) assay, cytotoxic T-lymphocyte (CTL) assay and phytohemagglutinin (PHA) blast formation assay. Results: In this UCBC transplantation model, the overall survival of the recipient mice was dose-dependent, and all surviving recipient mice were hematopoietic chimeras possessing all lineages. These allogeneic chimeras specifically rejected skin grafts from third-party C3H/He mice (rejection time; 9–16 days) while showing tolerance to skin grafts from both donor-type and recipient type, although with a significant delay in comparison to normal BALB/c mice (8–12 days) and C57BL/6 mice (9–11 days). Although accurate antibody responses of the allogeneic chimeras against TNP-KLH immunization were not anticipated, substantial amounts of TNP-specific IgG were detected in their sera. Interestingly, the level of TNP-specific IgM was significantly higher than that of normal BALB/c mice after TNP-KLH immunization, indicating retarded immunoglobulin class-switching in the allogeneic chimeras. The mechanism responsible for the antibody production by allogeneic chimeras still remains unclear. CTL and MLR assay revealed cell-mediated third-party-specific activity of killer and helper T cells, consistent with the tendency for the skin graft rejection and antibody production capability of the allogeneic chimeras to be inferior to those of normal mice. T cells of the allogeneic chimeras also proliferated non-specifically in response to PHA stimulation. The T-cell proliferation indices of the allogeneic chimeras when those of normal mice were taken as 100 were 21 in the MLR assay and 48 in the PHA blast formation assay, suggesting relative inferiority of the recognition and response system of T cells generated in an allogeneic environment. In any event, it may be important to note that T-dependent antigen-specific antibody production and alloantigen-specific rejection were substantial in the allogeneic chimeras. Conclusions: Overall, the present findings suggest that UCBC-derived lymphocytes generated in HLA-mismatched recipients are immunologically functional and competent. Regarding the relative inferiority of immune responses in the allogeneic chimeras, we predict the causes originate from narrowing of the T- and B-cell receptor repertoire by the allogeneic environment, and this possibility is now being examined. Disclosures: No relevant conflicts of interest to declare.
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Shegarfi, Hamid, and Olav Reikeras. "Review Article: Bone Transplantation and Immune Response." Journal of Orthopaedic Surgery 17, no. 2 (August 2009): 206–11. http://dx.doi.org/10.1177/230949900901700218.
Повний текст джерелаАнотація:
Bone is the second most common transplant tissue after blood, with the iliac crest autologous graft being most used. Bone transplantation induces osteogenesis to repair bone defects. Despite being the most efficient, autogenous bone requires an additional incision and its supply may be inadequate. Deep-frozen allogeneic bone can be an alternative, but is at risk of microbiological contamination, transmission of unrecognised germs, delayed incorporation, and cellular and humoral immune reactions. Synthetic graft substitutes combine scaffolding properties with biological elements to stimulate cell proliferation and differentiation and eventually osteogenesis. However, they generally lack osteoinductive or osteogenic properties and have various effects on bone healing. We present an overview of bone grafts and graft substitutes in clinical use, and the immune responses to allogeneic bone.
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Moses, R. D., R. N. Pierson, H. J. Winn, and H. Auchincloss. "Xenogeneic proliferation and lymphokine production are dependent on CD4+ helper T cells and self antigen-presenting cells in the mouse." Journal of Experimental Medicine 172, no. 2 (August 1, 1990): 567–75. http://dx.doi.org/10.1084/jem.172.2.567.
Повний текст джерелаАнотація:
We studied proliferation and interleukin 2 production by B6 mouse spleen cells in response to stimulation by irradiated cynomolgus monkey spleen cells and compared the results with responses against whole MHC-disparate allogeneic controls (BALB/c). We found that (a) primary xenogeneic helper responses were absent, whereas primary allogeneic responses were brisk, (b) secondary xenogeneic helper responses were dependent on CD4+ T cells and responder antigen-presenting cells (APCs), whereas allogeneic responses could be mediated by either CD4+ or CD8+ T cells independently and were primarily dependent on the presence of stimulator APCs, and (c) secondary xenogeneic helper responses were blocked by an antibody directed against responder class II MHC molecules. These results suggest that mouse helper T cells recognize disparate xenoantigens as processed peptides in association with self class II MHC molecules, similar to the recognition of nominal antigens and unlike direct allo-recognition.
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Avall, Anders, Monica Hyllner, Jan Peter Bengtson, Lars Carlsson, and Anders Bengtsson. "Postoperative Inflammatory Response after Autologous and Allogeneic Blood Transfusion." Anesthesiology 87, no. 3 (September 1, 1997): 511–16. http://dx.doi.org/10.1097/00000542-199709000-00009.
Повний текст джерелаАнотація:
Background Allogeneic blood transfusions cause immunosuppression. The aim of this study was to determine whether complement anaphylatoxins, cytokines, or both are released in the recipient, after blood transfusions in general, and after autologous blood transfusions in particular. Methods Thirty-one patients having total hip joint replacement surgery were randomized to receive either allogeneic red blood cells (n = 15) or predeposited autologous whole blood transfusion (n = 16). Plasma concentrations of the anaphylatoxins C3a and C5a, the terminal C5b-9 complement complex, and cytokines IL-6 and IL-8 in the recipients were repeatedly analyzed before, during, and after surgery. Results Significantly increased concentrations of IL-6 and IL-8 appeared in both groups, with a significantly greater increase in the autologous blood group. Patients in both groups developed a moderate but significant increase of C3a without a significant difference between them. C5a and terminal C5b-9 complement complex were not greatly changed. Conclusions The study showed a greater increase in cytokine concentration after autologous blood transfusion than after allogeneic blood transfusion. The lower response in the latter may result from transfusion-induced suppression of cellular immunity.
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Sayeh, Ebrahim, Katherine Sterling, Edwin Speck, John Freedman та John W. Semple. "IgG antiplatelet immunity is dependent on an early innate natural killer cell–derived interferon-γ response that is regulated by CD8+ T cells". Blood 103, № 7 (1 квітня 2004): 2705–9. http://dx.doi.org/10.1182/blood-2003-10-3552.
Повний текст джерелаАнотація:
Abstract The mechanisms responsible for immunoglobulin G (IgG) immunity against allogeneic platelets are poorly understood. We studied the role that murine recipient CD8+ T and natural killer (NK) cells play in immunity against allogeneic platelets. BALB/c mice were depleted of the cells by cell-specific antibodies, transfused weekly with platelets from C57BL/6 mice, and serum IgG antidonor antibodies were measured by flow cytometry. While allogeneic platelet transfusions into wild-type recipients stimulated IgG antidonor antibodies in all mice by the fifth transfusion, CD8-depleted mice had significantly (P < .001) enhanced antibody production. Isotype analysis revealed that CD8+ T cells suppressed T-helper 2 (Th2)-associated IgG1 but enhanced Th1-associated IgG2a. Compared with wild-type mice, platelet transfusions into CD8-depleted mice stimulated enhanced intracellular interferon (IFN)-γ production by CD4- lymphocytes within 24 hours after the first transfusion. The early IFN-γ response correlated with nitric oxide-dependent splenic cytotoxicity (P < .001). In asialo ganglioside monosialic acid 1 (GM1)-depleted mice transfused with allogeneic platelets, the IFN-γ production, splenic cytotoxicity, and IgG antidonor antibody response were significantly suppressed. These results demonstrate that IgG antiplatelet immunity is dependent on an early NK cell-derived IFN-γ response that is negatively regulated by CD8+ T cells and suggest that targeting innate NK cell responses may significantly reduce platelet alloimmunization. (Blood. 2004;103:2705-2709)
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Tomkinson, B. E., R. Maziarz, and J. L. Sullivan. "Characterization of the T cell-mediated cellular cytotoxicity during acute infectious mononucleosis." Journal of Immunology 143, no. 2 (July 15, 1989): 660–70. http://dx.doi.org/10.4049/jimmunol.143.2.660.
Повний текст джерелаАнотація:
Abstract Primary infection with EBV during acute infectious mononucleosis (IM) is associated with a cytotoxic response against allogeneic target cells. C depletion with anti-CD3 (OKT3) and anti-CD8 (OKT8) mAb decreased the allogeneic cytolysis of two EBV-infected lymphoblastoid cell lines (LCL) by 96% and 89%, respectively. Complement depletion with the NK cell-specific mAb Leu-11b and NKH-1a resulted in only a slight decrease (less than 35%) in the lysis of these LCL. mAb inhibition studies with OKT3 and OKT8 inhibited the allogeneic lysis of two LCL by 87% and 82%, respectively. The alloreactive cytotoxic response was strongly inhibited by mAb specific for MHC class I determinants (W6/32, 65% inhibition and BBM.1, 58% inhibition). Acute IM lymphocytes lysed the allogeneic EBV-negative cell lines HSB2 (45%) and HTLV-1 T cell lines (16%). NK cell-depleted lymphocytes from an acute IM patient demonstrated preferential lysis of K562 transfected with human HLA-A2 (73%) compared with the K562 transfected control (20%). Cold target competition studies with allogeneic and autologous target and competitor LCL demonstrated no significant competitive inhibition between allogeneic and autologous cells. We interpret these results as evidence that 1) the acute IM-alloreactive cytotoxic response is mediated primarily by CTL; 2) these alloreactive CTL lyse allogeneic target cells irrespective of EBV antigenic expression; 3) MHC class I expression is sufficient for allogeneic recognition and lysis of target cells; 4) distinct effector CTL populations mediate lysis of autologous and allogeneic target cells; and 5) during acute IM, EBV infection results in the induction of both virus-specific and alloreactive CTL populations.
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Attolico, Imma, Francesco Tarantini, Paola Carluccio, Claudia Schifone, Mario Delia, Vito Pier Gagliardi, Tommasina Perrone, et al. "Serological Response Following BNT162b2 Anti-Sars-Cov-2 mRNA Vaccination in Hematopoietic Stem Cell Transplantation Patients." Blood 138, Supplement 1 (November 5, 2021): 4875. http://dx.doi.org/10.1182/blood-2021-147542.
Повний текст джерелаАнотація:
Abstract Patients with hematological malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) have an increased vulnerability to SARS-Cov-2 (Sharma et al, Lancet Haematology 2020; Ljungman et al, Leukemia 2021), the reason why international guidelines strongly support the need for a protective vaccination for these subjects. The most relevant data currently available on the response to a complete anti-SARS-Cov-2 vaccination cycle in HM patients after HSCT refer to 314 patients reported in a Lithuanian national survey (Maneikis et al, Lancet Haematol 2021). In this study, the median titers of antibodies against SARS-Cov-2, determined 7-21 days after the second vaccination, were comparable to that of healthy controls (HC) in both autologous and allogeneic groups, with no patient found below the protective threshold of 50 arbitrary units (AU)/ml. Notably, the large majority of patients had received the transplant more than 1 year before vaccination. In a prospective, cohort study, we compared 114 patients, who had received an autologous or allogeneic HSCT at least three months before the first dose of vaccination, to 107 HC, matched for age and sex. Study population and HC received two doses of BNT162b2 anti-SARS-Cov-2 mRNA vaccine on days 1 and 21, between April and May 2021. Serological tests were performed by a commercially available immunoassay for the quantitative determination of anti-spike IgG antibodies to SARS-Cov-2. The cut-off for defining responders was 50 or greater AU/ml. Patients and HC samples were collected four weeks after the second dose of the vaccine. Table 1 reports the main clinical characteristics of patients and HC. Eighteen of 114 patients (16%) did not respond (24% in the allogeneic group, 6% in autologous recipients). Overall, median antibodies titers did not differ between HC and the entire cohort of transplanted patients, recipients of allogeneic HSCT, all patients responding to the vaccine or responders in the autologous subgroup (Figure 1A). All autologous HSCT recipients had significantly lower titers of antibodies than HC, while higher levels were found in responders who had received allogeneic HSCT (Figure 1A). Responders in the allogeneic subgroup showed antibodies titers significantly higher than responders in the autologous subgroup (Figure 1B). We further stratified patients in three groups, according to the time elapsed from transplant to vaccination: G1:<1 year; G2:1-5 years; G3:>5 years. Higher antibodies titers were observed in HC compared to all transplanted patients in G1 (Figure 1C), including both allogeneic (Figure 1D) and autologous (Figure 1E) HSCT recipients. No differences emerged in G2 between HC and all patients (Figure 1C), allogeneic (Figure 1D) or autologous (Figure 1E) HSCT recipients. Finally, no differences were found in G3 when comparing HC with all patients (Figure 1C) or allogeneic recipients (Figure 1D), whereas patients in the autologous subgroup showed significantly lower titers than HC (Figure 1E). Myeloma patients with controlled disease showed higher titers than patients with active disease (Figure 1F). According to median age, autologous HSCT recipients older than 57 years had significantly lower antibody levels than younger patients (Figure 1G). Autologous vs allogeneic HSCT, age of all patients and of allogeneic HSCT recipients, sex, type of allogeneic HSCT, conditioning regimen, age and sex of donor, occurrence of GVHD, disease type and single vs double autologous HSCT did not significantly impact on antibody levels (data not shown). No relevant side effects were recorded after vaccination. With a median follow up of 12 weeks, no case of COVID19 occurred among vaccinated patients. In our single center study, patients with a previous history of HSCT tolerated well BNT162b2 vaccine and mounted a potentially protective immune response in the majority of cases one month after two doses of vaccine. However, lack of response was not rare, especially in the allogeneic setting. The main factor associated with the quality of response was the time from HSCT, with lower responses within the first year from transplant and differences between autologous and allogeneic groups transplanted more than five years before vaccination. Here, a consolidated, complete immune reconstitution in allogeneic HSCT recipients, as well as age and a still active disease in the autologous setting, could have played opposite pivotal roles. Figure 1 Figure 1. Disclosures Delia: Gilead: Consultancy; Amgen: Consultancy; abbvie: Consultancy; Jazz pharmaceuticals: Consultancy.
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Zecher, Daniel, Nico van Rooijen, David M. Rothstein, Warren D. Shlomchik, and Fadi G. Lakkis. "An Innate Response to Allogeneic Nonself Mediated by Monocytes." Journal of Immunology 183, no. 12 (November 18, 2009): 7810–16. http://dx.doi.org/10.4049/jimmunol.0902194.
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Grzelak, I., M. Zaleska, and W. L. Olszewski. "Immune response after syngeneic and allogeneic blood cell transplantation." Transplantation Proceedings 29, no. 4 (June 1997): 2181–82. http://dx.doi.org/10.1016/s0041-1345(97)00283-2.
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BUMGARDNER. "In vivo immune response to allogeneic (ALLO) hepatocytes (HC)." Cell Transplantation 5, no. 5 (September 1996): 33. http://dx.doi.org/10.1016/0963-6897(96)82172-5.
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GRZELAK. "Immune response after syngeneic and allogeneic blood cell transplantation." Cell Transplantation 5, no. 5 (September 1996): 63. http://dx.doi.org/10.1016/0963-6897(96)82265-2.
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Peshwa, Madhusudan V., Claudia Bemke, Marc Dupuis, Smriti K. Kundu, Edgar G. Engleman, Thomas C. Merigan, and Wim C. A. Van Schooten. "Generation of Primary Peptide-Specific Cd8+ Cytotoxic T-lymphocytes in Vitro using allogeneic dendritic cells." Cell Transplantation 7, no. 1 (January 1998): 1–9. http://dx.doi.org/10.1177/096368979800700103.
Повний текст джерелаАнотація:
Dendritic ceils (DC) are potent antigen-presenting cells (APC) capable of inducing strong T-cell–mediated immunity. Infusion of lymphoma-specific antigen-loaded autologous DC has been demonstrated to result in the generation of antigen-specific immunity and reduction in tumor burden in B-cell lymphoma patients. Cellular immunotherapy employing antigen-loaded DC could have a potential therapeutic impact in tumors and viral infections, including HIV infection. However, DC in HIV-infected individuals and breast cancer patients are believed to be functionally defective. Therefore, the potential of using allogeneic DC offers significant implications for DC immunotherapy in AIDS and immunocompromised cancer patients. To explore the potential of allogeneic DC therapy in vivo, we tested the ability of allogeneic DC to generate primary peptide-specific CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro. Our results indicate that DC from HLA class I-matched individuals elicit primary immune responses in vitro using viral peptides as naive antigens. A primary peptide-specific immune response could also be detected even when only one HLA allele (HLA-A*0201) was matched between the allogeneic DC and T-lymphocytes. The ability to generate primary peptide-specific responses in vitro is strongly indicative of the in vivo therapeutic potential of allogeneic DC.
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Nauta, Alma J., Geert Westerhuis, Alwine B. Kruisselbrink, Ellie G. A. Lurvink, Roel Willemze, and Willem E. Fibbe. "Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting." Blood 108, no. 6 (September 15, 2006): 2114–20. http://dx.doi.org/10.1182/blood-2005-11-011650.
Повний текст джерелаАнотація:
AbstractMesenchymal stem cells (MSCs) are multipotent progenitor cells that have emerged as a promising tool for clinical application. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more important, display immunosuppressive capacities. These properties may be of therapeutic value in allogeneic transplantation to prevent graft rejection and to prevent and treat graft-versus-host disease. In the present study, we examined the in vivo immunomodulatory properties of MSCs in murine models of allogeneic bone marrow (BM) transplantation. Sublethally irradiated recipients received allogeneic BM with or without host or donor MSCs. The addition of host MSCs significantly enhanced the long-term engraftment associated with tolerance to host and donor antigens. However, the infusion of donor MSCs was associated with significantly increased rejection of allogeneic donor BM cells. Moreover, we showed that the injection of merely allogeneic donor MSCs in naive mice was sufficient to induce a memory T-cell response. Although the observed engraftment-promoting effects of host MSCs in vivo support the therapeutic potential of MSCs, our results also indicate that allogeneic MSCs are not intrinsically immunoprivileged and that under appropriate conditions, allogeneic MSCs induce a memory T-cell response resulting in rejection of an allogeneic stem cell graft.
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Ahlmann, Alexander Høgsted, Shu Fang, Sussi Bagge Mortensen, Line Weis Andersen, Pernille Gejl Pedersen, Johanne Juel Callesen, Sara Thornby Bak, Kate Lykke Lambertsen, and Ditte Caroline Andersen. "Decellularised Human Umbilical Artery as a Vascular Graft Elicits Minimal Pro-Inflammatory Host Response Ex Vivo and In Vivo." International Journal of Molecular Sciences 22, no. 15 (July 26, 2021): 7981. http://dx.doi.org/10.3390/ijms22157981.
Повний текст джерелаАнотація:
Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. Decellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and confirmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day −7 to 28). Likewise, we found no difference in systemic inflammatory and anti-inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro-inflammatory response further supporting its use as a TEVG in an allogeneic setup.
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Fast, Loren D., Alejandro Pando, and John L. Reagan. "Harnessing alloreactive responses by patient lymphocytes to achieve anti-cancer responses." Journal of Immunology 202, no. 1_Supplement (May 1, 2019): 136.26. http://dx.doi.org/10.4049/jimmunol.202.supp.136.26.
Повний текст джерелаАнотація:
Abstract Potent immune responses are induced by encounter with cells from a different (allogeneic) individual. The increased number of responding alloreactive T cells can be explained by the cross-reactivity exhibited by T cell receptors (TCR). This cross-reactivity also allows these TCR to bind to syngeneic major histocompatibility complex molecules expressing peptides derived from pathogens or cancer cells. Initial studies showed that CD3+ lymphocytes isolated from newly diagnosed leukemic patients were able to lyse syngeneic leukemic cells after stimulation with allogeneic cells in about half of the patients. These findings raise the possibility that manipulating the alloreactive responses by patient lymphocytes could result in enhanced anti-cancer responses. Further studies utilized a mouse acute myeloid leukemic cell line, C1498, derived from a C57BL/6 mouse. C57BL/6 splenocytes stimulated with allogeneic stimulator cells were shown to be able to lyse allogeneic target cells as well as the syngeneic C1498 leukemic cells. The level of lysis of the syngeneic leukemic cells was dependent on the strain from which the allogeneic stimulator cells were obtained. Immunization of C57BL/6 mice with C1498 cells or subcellular antigen enhanced the anti-C1498 response when stimulated with allogeneic cells. Ongoing experiments are defining whether naïve or memory effector cells are responsible for the lysis of the syngeneic leukemic cells as well as the nature of the peptide antigens that allow the syngeneic cancer cells to be recognized. The results of these studies will facilitate the use of protocols which harness alloreactive responses by patient lymphocytes to generate anti-cancer responses.
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Zarling, Angela L., Julia G. Johnson, Robert W. Hoffman, and David R. Lee. "Induction of Primary Human CD8+ T Lymphocyte Responses In Vitro Using Dendritic Cells." Journal of Immunology 162, no. 9 (May 1, 1999): 5197–204. http://dx.doi.org/10.4049/jimmunol.162.9.5197.
Повний текст джерелаАнотація:
Abstract The ability of two different human professional APCs, specifically macrophages (Mφ) and dendritic cells (DC), to stimulate primary responses in human CD8+ T lymphocytes was examined using both allogeneic and Ag-pulsed autologous APCs. CTL responses in CD8+ T lymphocytes isolated from HIV-uninfected donors were evaluated against six different HIV epitopes that are restricted by four different HLA alleles using autologous human PBMC-derived Mφ and DCs for primary stimulation. In a side-by-side experiment, immature DCs, but not Mφ, were able to prime a CTL response against the B14-restricted p24gag 298–306 epitope; mature DCs were also able to prime a response against this epitope. In addition, DCs were capable of priming CD8+ CTL responses against the B8-restricted p24gag 259–267 epitope. In contrast, Mφ were unable to prime strong CTL responses against other epitopes. Since the Ag-specific cytotoxic responses required subsequent rounds of restimulation before they could be detected, the ability of the allogeneic Mφ and DCs to directly prime CD8+ T lymphocyte responses without subsequent restimulation was examined. Similar to the aforementioned peptide-specific results, DCs were more efficient than Mφ in priming both allogeneic proliferative and cytotoxic responses in human CD8+ T lymphocytes. Collectively, these results promote an enhanced status for DCs in the primary stimulation of human CD8+ T lymphocytes.
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Wu, Douglas, and Kathryn Wood. "An analysis of the adaptive immune response towards an embryonic stem cell grafts." Clinical & Investigative Medicine 30, no. 4 (August 1, 2007): 98. http://dx.doi.org/10.25011/cim.v30i4.2879.
Повний текст джерелаАнотація:
Background: Although clinical transplantation has had enormous impact on the treatment of premature organ failure, shortage of donor organs continues to be a crucial limiting factor. Embryonic stem cells represent an attractive potential source of replacement tissue because of their inherent pluripotentiality and ability to self-renew. However, before any ES cell-based cellular replacement strategies can be considered, many issues must be addressed. Among these is an evaluation of the potential immune response elicited by any ES cell graft. Because ES cells express very low levels of MHC class I and no MHC class II, their immunogenicity has been questioned. Here we utilize a BM3 TCR transgenic model to analyze the adaptive immune response against an ES cell graft in vivo.
Methods: BM3 CD8 TCR-tg T cells (H2K background) specific for the MHC class I molecule H2Kb were labelled with CFSE and adoptively transferred into CBA rag recipients. The following day, ES cells derived from a CBA, B6, or CBK background were implanted beneath the kidney capsule of adoptively transferred mice. Response of the CD8 T cells was measured via CSFE division profiling and graft infiltration.
Results: CFSE division profile of naïve BM3 CD8 T cells was unaltered by the presence of either a syngeneic or an allogeneic ES cell graft. These naïve cells were also unable to recognize and infiltrate either a syngeneic or allogeneic ES cell graft on days 5 and 10 post-implantation, despite strong expression of the MHC class I molecule H2Kb by engrafted allogeneic ES cells. On the other hand, H2Kb+ islets begun to be infiltrated by day 5, and were obliterated by a vigorous allogeneic response by day 10. When H2Kb+ islets were implanted into the same kidney as allogeneic ES cells (opposite poles), islet grafts were rapidly infiltrated by CD4 and CD8 T cells and destroyed, but ES cell grafts exhibited markedly reduced cellular infiltrate. In contrast to naïve BM3 CD8 T cells, however, activated cells recognized and mounted an aggressive cytotoxic response against an allogeneic ES cell graft which could be detected by day 6 and resulted in complete graft destruction by day 10.
Conclusions: Under certain circumstances, an ES cell graft may have reduced immunogenicity as compared with other conventional tissue or solid organ allografts. This may be due to their lack of passenger APC, which may in turn cripple their ability to elicit a robust allogeneic response via the direct pathway of allorecognition. However, because of their strong upregulation of allogeneic MHC class I molecules after transplantation, they are still likely to elicit a significant rejection response when transplanted into recipients replete with both CD4 and CD8 T cells.
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Beggs, Kirsten J., Elisabeth H. Javazon, Jessica C. Tebbets, and Alan W. Flake. "Evidence of Host Immune Recognition of Allogeneic Mesenchymal Stem Cells." Blood 104, no. 11 (November 16, 2004): 1287. http://dx.doi.org/10.1182/blood.v104.11.1287.1287.
Повний текст джерелаАнотація:
Abstract The immunologic properties of Mesenchymal Stem Cells (MSCs) are of therapeutic interest. Previous work shows MSCs do not elicit an alloreactive T cell response in vitro due to suppressive mechanisms. These results suggested that allogeneic MSCs could be used in vivo without inducing an immune response. We further explored this hypothesis using a well-characterized population of Adult Murine Mesenchymal Stem Cells (AmMSCs). These AmMSC are free of hematopoietic contamination and have the following immunologic phenotype: Class I +, Class II-, CD40-, CD80+, and CD86−. Upon treatment with interferon gamma, upregulation of Class I, Class II, CD80, and CD86 was observed. T cell proliferation assays were performed using CFDA SE tracking dye and T cell subsets were analyzed using dual color flow cytometry. The AmMSCs were capable of suppressing CD4+ and CD8+ T cell proliferation in response to alloantigen or polyclonal mitogen, independent of MHC matching, when cultured in direct contact with the T cells. Intracellular cytokine staining of CD4+ and CD8+ T cells revealed that interferon gamma and IL-10 production increased in co-cultures with AmMSC. This suggested that AmMSC are recognized by T cells, but are suppressing proliferation due to other mechanisms in vitro. In order to determine if donor AmMSCs are detected by an immunocompetent host in vivo, we conducted the following study. C57/B6 mice received an intraperitoneal injection of either one million C57/B6 GFP AmMSC (congenic, n=5), one million Balb/c AmMSC (allogeneic, n=5) , or 5 million Balb/c splenocytes (allogeneic control, n=5) at time point zero, and then were given an additional injection of the same cells at 4 weeks. Mice were bled at 0,2,4,5, and 6 weeks after the first injection. Serum was collected and assayed for alloantibody production. Alloantibody results revealed IgG and IgM responses against donor alloantigen at titers of greater than 1:100 in all 5 animals injected with Balb/c MSC. This was significantly increased over titers observed in the 5 mice injected with congenic C57/B6 GFP AmMSC, and similar to the titers seen in mice injected with allogeneic splenocytes. At six weeks post injection animals were sacrificed and a mixed lymphocyte reaction (MLR) was performed using host splenocytes as responders and irradiated donor splenocytes as stimulators. Splenocytes were stained using CFDA SE tracking dye and stained for CD4+ and CD8+ positive T cells. Proliferation of CD4+ and CD8+ T cells was measured using dual color flow cytometry. No increase in proliferation compared to a naïve MLR was noted in the animals injected with the congenic C57/B6 GFP AmMSCs. However all animals injected with allogeneic AmMSCs or allogeneic splenocytes showed increased CD4+ and CD8+ proliferation. It has been suggested primarily based on their in vitro properties, that MSCs may evade the immune response or induce tolerance after allogeneic transplantation. Our results document immune recognition of AmMSCs in vitro and in vivo. While we observed suppression of T-cell proliferation in vitro, our results after in vivo administration support a specific allogeneic immunization response equivalent to that induced by allogeneic splenocytes. These results argue against the theory that allogeneic MSCs may induce tolerance after transplantation, or that they can escape immune surveillance.
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MacKenzie, Tippi, Erin Jarvis, Amar Nijagal, Tom Le, Marta Wegorzewska, and Qizhi Tang. "The Maternal Immune Response to in Utero Hematopoietic Stem Cell Transplantation." Blood 114, no. 22 (November 20, 2009): 64. http://dx.doi.org/10.1182/blood.v114.22.64.64.
Повний текст джерелаАнотація:
Abstract Abstract 64 In utero hematopoietic stem cell transplantation (IUHSCTx) is a promising treatment strategy for many congenital hematopoietic disorders such as immunodeficiencies. However, clinical applications have been hampered by lack of engraftment, possibly secondary to a host immune response. This has been a conundrum in the field, since the fetus can also be tolerized to allogeneic cells in some circumstances. We hypothesized that it is the maternal immune response which limits engraftment of in utero transplanted cells. Methods: Fetal BALB/c mice at 14 days' gestation were transplanted with age-matched fetal liver (FL) cells (2.5 × 106 cells/fetus) from allogeneic C57B6 mice and levels of circulating donor cell chimerism were determined serially starting at 4 weeks after in utero transplantation. Rates of engraftment (number of chimeric pups/number of surviving pups) and levels of chimerism (donor CD45 cells/total CD45 cells) were compared to controls in which animals were transplanted with congenic cells (C57B6 (CD45.2) fetal hosts transplanted with C57B6 (CD45.1) FL). In order to determine the role of the maternal adaptive immune system, immunodeficient BALB/c.Rag−/− mothers (deficient in T and B cells) were bred to wild type BALB/c males, such that the fetuses (BALB/c.Rag+/−) would be immunocompetent. These fetuses were transplanted with C57B6 FL and rates of engraftment and levels of chimerism in these transplants were compared to those in wild type allogeneic transplants. In order to determine whether the maternal influence is caused by maternal lymphocytes trafficking into the fetus, C57B6 (CD45.2) females were bred to C57B6 (CD45.1) males, such that the fetal cells (CD45.1+/CD45.2+) could be distinguished from maternal cells (CD45.1−/CD45.2+). Fetal blood and tissues were examined for the presence of maternal cells by flow cytometry at various gestational ages. Results: The rate of engraftment after IUHSCTx in control animals transplanted with congenic cells was 14/16 (88%) and average levels of chimerism were 9.9±8.4%. In contrast, the rate of engraftment in wild-type BALB/c fetuses transplanted with allogeneic B6 cells was 11/25 (44%; p<0.05 compared to congenic), and levels of chimerism were 21±19 (p=NS), confirming there is an adaptive immune response to fetal stem cell transplantation. As expected, chimeric animals were tolerant to the donor strain by mixed lymphocyte reaction while injected, non-chimeric animals were sensitized. However, in the absence of a maternal adaptive immune system, rates of chimerism (in immunocompetent BALB/c.Rag+/− pups) increased to 100% (n=10, p<0.05 compared to wild type allogeneic) and levels of chimerism were significantly higher (44±18, p<0.05). Levels of chimerism in engrafted animals declined over time after allogeneic transplantation but not after congenic transplantation, indicating there is a second, late phase immune response to allogeneic cells. However, chimerism levels did not decline in the BALB/c.Rag+/− recipients, suggesting that the maternal immune system has long-lasting effects on the success of fetal transplantation, perhaps by priming the host immune system. In our analysis of maternal/fetal cellular trafficking, we detected maternal lymphocytes in the blood of midgestation fetuses (14±7% at E12.5–E14.5, n=9) which declined gradually and was undetectable after birth. Lineage analysis demonstrated that 45±15 % of maternal cells are Gr-1+ granulocytes and 21±15% are B cells. Trafficking of maternal cells into the fetus was increased following fetal manipulation (injection of PBS < injection of allogeneic HSC). Conclusions: There is an adaptive immune response which limits early engraftment after in utero transplantation of allogeneic cells and leads to a gradual decline in levels of chimerism in engrafted animals. However, in the selective absence of maternal T and B cells, all fetuses transplanted with allogeneic FL cells show long-term, multilineage engraftment and demonstrate donor-specific tolerance. These results indicate that the maternal immune system plays a significant role in the success of fetal HSC transplantation. Cellular trafficking between the mother and fetus may be a mechanism by which maternal lymphocytes encounter cells transplanted into the fetus. Our findings have clinical implications in that the success of IUHSCTx may be improved by harvesting cells from the mother or HLA-matching cells to the mother. Disclosures: No relevant conflicts of interest to declare.
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Beguin, Y., GK Clemons, R. Oris, and G. Fillet. "Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants." Blood 77, no. 4 (February 15, 1991): 868–73. http://dx.doi.org/10.1182/blood.v77.4.868.868.
Повний текст джерелаАнотація:
Abstract We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT.
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Beguin, Y., GK Clemons, R. Oris, and G. Fillet. "Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants." Blood 77, no. 4 (February 15, 1991): 868–73. http://dx.doi.org/10.1182/blood.v77.4.868.bloodjournal774868.
Повний текст джерелаАнотація:
We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT.
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Tang, M. L., L. P. Hale, D. A. Steeber, and T. F. Tedder. "L-selectin is involved in lymphocyte migration to sites of inflammation in the skin: delayed rejection of allografts in L-selectin-deficient mice." Journal of Immunology 158, no. 11 (June 1, 1997): 5191–99. http://dx.doi.org/10.4049/jimmunol.158.11.5191.
Повний текст джерелаАнотація:
Abstract Adhesion of leukocytes to vascular endothelium is crucial for leukocyte migration into tissues. The contributions of L-selectin, P-selectin, and ICAM-1 to interactions between lymphocytes and endothelium was examined using allogeneic skin graft rejection as a model of cutaneous inflammation. L-selectin-deficient (L-selectin(-/-)) mice rejected both primary and secondary allogeneic (BALB/c) skin grafts significantly more slowly than L-selectin(+/+) littermates. Furthermore, skin graft rejection remained significantly delayed in L-selectin(-/-) mice, despite placement of grafts 7 days after i.p. immunization with allogeneic cells, when CTL responses in L-selectin(-/-) mice and L-selectin(+/+) littermates were confirmed to be equivalent. Indeed, specific CTL responses to BALB/c splenocytes were normal or elevated in L-selectin(-/-) mice following either skin grafts or immunization. However, the number of T lymphocytes within allogeneic grafts was lower in L-selectin(-/-) mice as compared with L-selectin(+/+) littermates. Therefore, delayed rejection of skin grafts by L-selectin(-/-) mice reflects impaired migration of effector cells into the graft rather than delayed or impaired generation of a CTL response. In contrast to L-selectin(-/-) mice, P-selectin-deficient and ICAM-1-deficient mice rejected allogeneic skin grafts normally. These findings delineate an important role for L-selectin in lymphocyte recruitment to cutaneous sites of inflammation.
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Waldschmidt, Thomas J., Angela Panoskaltsis-Mortari, Ronald T. McElmurry, Lorraine T. Tygrett, Patricia A. Taylor, and Bruce R. Blazar. "Abnormal T cell–dependent B-cell responses in SCID mice receiving allogeneic bone marrow in utero." Blood 100, no. 13 (December 15, 2002): 4557–64. http://dx.doi.org/10.1182/blood-2002-04-1232.
Повний текст джерелаАнотація:
In allogeneic hematopoietic stem cell transplant recipients, restoration of humoral immunity is delayed and can remain impaired for years. In many severe combined immune deficiency (SCID) patients given haploidentical bone marrow (BM), lesions in humoral immunity are exacerbated by poor engraftment of donor B cells. The nature of these defects is important to understand as they render patients susceptible to infection. Previous work in mice suggested that in utero transplantation (IUT) of allogeneic BM might offer several advantages for the correction of primary immune deficiencies. In SCID mice given fully allogeneic BM in utero, the lymphoid compartment was restored with minimal evidence of graft-versus-host disease (GVHD). The present report examines B-cell reconstitution and function in mice that have received allogeneic IUT. Results are compared with those of adult mice given total body irradiation (TBI) followed by transplantation with allogeneic BM. In addition to enumerating the various B-cell subsets present in BM, spleen, and peritoneal cavity (PC), B-cell competence was assessed by challenging mice with T cell–independent (TI) and T cell–dependent (TD) antigens. The results demonstrated that all B-cell subsets in the BM and periphery were restored in allogeneic IUT and TBI mice, as were antibody responses after TI challenge. Upon immunization with TD antigens, however, IUT and TBI mice exhibited suboptimal responses as measured by the capacity to isotype switch and generate germinal center (GC) B cells. Thus, although allogeneic BM transplantation results in complete recovery of the B-cell compartment, certain elements of the humoral response remain defective.