Journal articles: 'Transplantation immunology; Cellular rejection'

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Korsgren, Olle. "Acute cellular xenograft rejection." Xenotransplantation 4, no. 1 (February 1997): 11–19. http://dx.doi.org/10.1111/j.1399-3089.1997.tb00159.x.

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Bolton, E. M., J. A. Gracie, J. D. Briggs, J. Kampinga, and J. A. Bradley. "Cellular requirements for renal allograft rejection in the athymic nude rat." Journal of Experimental Medicine 169, no. 6 (June 1, 1989): 1931–46. http://dx.doi.org/10.1084/jem.169.6.1931.

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This study has examined the ability of adoptively transferred CD4+ and CD8+ T cells to mediate rejection of a fully allogeneic DA renal graft in the PVG nude rat. Transfer, at the time of transplantation, of naive CD4+ T cells caused rapid graft rejection and primed CD4+ cells were several times more potent. In contrast, naive or specifically sensitized CD8+ cells were entirely ineffective at mediating renal allograft rejection. Whereas nonrejecting grafts showed only a mild cellular infiltrate, rejecting grafts in CD4+ reconstituted animals showed a substantial infiltrate and many of the infiltrating cells had a phenotype (MRC OX8+, MRC OX19-), consistent with NK cells. Experiments using a mAb (HIS 41) against an allotypic determinant of the leukocyte common antigen confirmed that the majority (greater than 80%) of the cellular infiltrate in rejecting grafts derived from the host rather than from the CD4+ inoculum. Infiltrating mononuclear cells, obtained from rejecting allografts 7 d after transplantation in CD4+-injected PVG nude hosts, showed high levels of in vitro cytotoxicity against not only kidney donor strain Con A blasts but also third-party allogeneic Con A blasts, as well as against both NK and LAK susceptible targets. When splenocytes from nontransplanted nude PVG rats were tested in vitro they also demonstrated high levels of lytic activity against both NK and LAK susceptible targets as well as allogeneic Con A blasts, which were not susceptible to lysis by spleen cells from euthymic rats. These findings suggest that injected CD4+ cells may cause renal allograft rejection by the recruitment of extrathymically derived, widely alloreactive cells into the kidney in this model of graft rejection.

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Pinchuk, A. V., R. V. Storozhev, I. V. Dmitriev, N. V. Shmarina, G. A. Nefedova, R. Sh Muslimov, and Yu S. Teterin. "Cellular rejection of pancreaticoduodenal graft." Russian Journal of Transplantology and Artificial Organs 20, no. 3 (September 17, 2018): 80–86. http://dx.doi.org/10.15825/1995-1191-2018-3-80-86.

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Aim. The evaluation of donor’s duodenum histological examination in diagnosis of pancreaticoduodenal graft rejection.Materials and methods. The 35-yo patient with terminal diabetic nephropathy undergone simultaneous retroperitoneal kidney and pancreas transplantation with enteric exocrine drainage of the graft via inter-duodenal anastomosis. When performing the esophagogastroduodenoscopy 2 years posttransplant we implemented histologic examination of the duodenum of the graft.Results. We diagnosed and verified severe cellular rejection of pancreaticoduodenal graft. Successful etiopathogenetic treatment of acute rejection of the graft (pulse therapy with glucocorticoids) was performed.Discussion. The diagnostic value of donor’s duodenum morphological examination in the diagnosis of pancreaticoduodenal graft rejection, the efficacy of anti-rejection treatment were performed in this case.

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Mandel, T. E., J. Kovarik, M. Koulmanda, and H. M. Georgiou. "Cellular rejection of fetal pancreas grafts: Differences between alio- and xenograft rejection." Xenotransplantation 4, no. 1 (February 1997): 2–10. http://dx.doi.org/10.1111/j.1399-3089.1997.tb00158.x.

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Sindhi, Rakesh, Chethan Ashokkumar, and Brandon W. Higgs. "Cellular alloresponses for rejection-risk assessment after pediatric transplantation." Current Opinion in Organ Transplantation 16, no. 5 (October 2011): 515–21. http://dx.doi.org/10.1097/mot.0b013e32834a94e3.

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Thude, Hansjörg, Petra Tiede, Martina Sterneck, Sven Peine, Björn Nashan, and Martina Koch. "CD28 gene polymorphisms and acute cellular rejection after liver transplantation." Human Immunology 81, no. 12 (December 2020): 675–78. http://dx.doi.org/10.1016/j.humimm.2020.10.002.

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Fryer, Jonathan P., Joseph R. Leventhal, Agustin P. Dalmasso, Sally Chen, Pamela A. Simone, Jose Jessurun, Lin Hong Sun, Nancy L. Reinsmoen, and Arthur J. Matas. "Cellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer." Transplant Immunology 2, no. 2 (June 1994): 87–93. http://dx.doi.org/10.1016/0966-3274(94)90033-7.

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Koutsokera, Angela, Liran Levy, Prodipto Pal, Ani Orchanian-Cheff, and Tereza Martinu. "Acute Cellular Rejection: Is It Still Relevant?" Seminars in Respiratory and Critical Care Medicine 39, no. 02 (March 26, 2018): 181–98. http://dx.doi.org/10.1055/s-0037-1617424.

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AbstractDespite significant progress in the field of transplant immunology, acute cellular rejection (ACR) remains a very frequent complication after lung transplantation (LTx), with almost 30% of LTx recipients experiencing at least one episode of treated ACR during the first year of follow-up. Most episodes respond to the first-line immunosuppressive treatment and are rarely a direct cause of death. However, the association of ACR with later adverse outcomes, such as chronic lung allograft dysfunction, bronchial stricture, and infectious complications associated with the intensification of immunosuppression, negatively impacts long-term survival. The burden imposed on patients and health-care resources is even higher in cases of refractory or recurrent ACR, which accelerates lung function decline. Although important laboratory and clinical research conducted over the last two decades has improved our understanding of the mechanisms underlying ACR, there are still many uncertainties about the risk factors for ACR, the optimal monitoring strategies, and the prediction of long-term outcomes. These knowledge gaps contribute to the large variability in clinical practice among LTx centers, which renders multicenter studies of ACR challenging. In this review, we summarize current evidence on the epidemiology, pathogenesis, and risk factors of ACR. We describe diagnostic and therapeutic approaches that are currently used in the clinical practice and also review promising diagnostic tools that are under investigation. Associations between ACR and other adverse outcomes of LTx are examined. Finally, within each topic of discussion, we highlight the main areas of controversy and opportunities for future research.

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Kumar, Senthil, Nihar Mohapatra, Deeplaxmi Purushottam Borle, Ashok Choudhury, Shashwat Sarin, and Ekta Gupta. "Non invasive diagnosis of acute cellular rejection after liver transplantation – Current opinion." Transplant Immunology 47 (April 2018): 1–9. http://dx.doi.org/10.1016/j.trim.2018.02.002.

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Keßler, B., M. Kurome, N. Klymiuk, A. Wünsch, J. Seissler, and E. Wolf. "New transgenic pigs for xenotransplantation, part 2: Strategies to overcome cellular rejection." Xenotransplantation 18, no. 1 (January 2011): 65. http://dx.doi.org/10.1111/j.1399-3089.2010.00607_7.x.

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Doran, T. J., L. Derley, A. Keogh, and P. Spratt. "Correlation of HLA antibodies to degree of cellular rejection in heart transplantation." Human Immunology 40 (January 1994): 124. http://dx.doi.org/10.1016/0198-8859(94)91906-2.

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Mori, Akihiro, Soichiro Murata, Nao Tashiro, Tomomi Tadokoro, Satoshi Okamoto, Ryo Otsuka, Haruka Wada, et al. "Establishment of Human Leukocyte Antigen-Mismatched Immune Responses after Transplantation of Human Liver Bud in Humanized Mouse Models." Cells 10, no. 2 (February 23, 2021): 476. http://dx.doi.org/10.3390/cells10020476.

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Humanized mouse models have contributed significantly to human immunology research. In transplant immunity, human immune cell responses to donor grafts have not been reproduced in a humanized animal model. To elicit human T-cell immune responses, we generated immune-compromised nonobese diabetic/Shi-scid, IL-2RγKO Jic (NOG) with a homozygous expression of human leukocyte antigen (HLA) class I heavy chain (NOG-HLA-A2Tg) mice. After the transplantation of HLA-A2 human hematopoietic stem cells into NOG-HLA-A2Tg, we succeeded in achieving alloimmune responses after the HLA-mismatched human-induced pluripotent stem cell (hiPSC)-derived liver-like tissue transplantation. This immune response was inhibited by administering tacrolimus. In this model, we reproduced allograft rejection after the human iPSC-derived liver-like tissue transplantation. Human tissue transplantation on the humanized mouse liver surface is a good model that can predict T-cell-mediated cellular rejection that may occur when organ transplantation is performed.

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Ashton-Chess, Joanna, Jean-Christian Roussel, Rafael Manez, Carmen Ruiz, Anne Moreau, Emanuele Cozzi, David Minault, Jean-Paul Soulillou, and Gilles Blancho. "Cellular participation in delayed xenograft rejection of hCD55 transgenic pig hearts by baboons." Xenotransplantation 10, no. 5 (August 27, 2003): 446–53. http://dx.doi.org/10.1034/j.1399-3089.2003.00018.x.

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Keßler, Barbara, Elisabeth H. Weiss, Benjamin G. Lilienfeld, Sigrid Müller, Elfriede Müller, Nadja Herbach, Rüdiger Wanke, et al. "Strategies to overcome cellular rejection of pig-to-primate xenografts - the next steps." Xenotransplantation 14, no. 4 (July 2007): 371–72. http://dx.doi.org/10.1111/j.1399-3089.2007.00418_12.x.

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Hanajiri, Ryo, Makoto Murata, Kyoko Sugimoto, Miho Murase, Haruhiko Ohashi, Tatsunori Goto, Keisuke Watanabe, et al. "Cord Blood Allograft Rejection Mediated By Coordinated Donor-Specific Cellular and Humoral Immune Processes." Blood 122, no. 21 (November 15, 2013): 4459. http://dx.doi.org/10.1182/blood.v122.21.4459.4459.

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Recent statistical analyses of the clinical outcome have revealed that the presence of donor-specific anti-HLA antibodies (DSAs) in pre-transplant recipient is correlated with increased risk for graft rejection after allogeneic hematopoietic stem cell (HSC) transplantation. However, while cytotoxic T lymphocytes (CTLs) recognizing mismatched HLA molecule of the donor have been shown to be involved in graft rejection, there has been no biological evidence in humans that graft rejection is mediated by DSAs. In the present study, we demonstrate a case of cord blood allograft rejection in which DSAs acted to mediate graft rejection. Interestingly, CTL clones specific for donor HLA molecule were also isolated, suggesting that humoral and cellular immune responses were together responsible for allograft rejection. A patient with graft rejection after HLA-mismatched cord blood transplantation was studied. The white blood cell count increased transiently, subsequently decreased to undetectable level, and finally graft rejection was diagnosed on day 34. Screening for pre-transplant anti-HLA antibodies was not routinely performed at that time. We initially presumed that DSA would be responsible for graft rejection. The patient serum on day 36 were screened for HLA antibodies and further evaluated to determine HLA specificities using a LABScreen Single Antigen Kit. An antibody against HLA-B* 54:01, which was expressed in donor cells but not in patient cells, was detected. To test the effect of the DSA against HLA-B* 54:01 on HSC engraftment, antibody-dependent cellular cytotoxicity (ADCC) activity was assessed using unrelated HLA-B* 54:01-positive bone marrow mononuclear cells (BMMNCs) pre-cultured with patient serum and pre-transplant NK cells. The patient serum clearly showed an inhibitory effect on colony formation. Complement-dependent cytotoxicity activity of the DSA could not be detected. These data suggest that the DSA impaired the cord blood engraftment through ADCC activities. We next determined if cellular immunity was also responsible for allograft rejection. Two independent CTL clones, CD4-CD8+ and CD4+CD8-, were isolated from the patient blood at the time of graft rejection by limiting dilution. Both CTL clones were of patient origin by using short tandem repeat analysis and showed cytotoxicity against donor cells but not patient cells in Cr release assay. A CTL stimulation assay using COS cells transfected with various mismatched donor HLA cDNA constructs demonstrated that CD8+ and CD4+CTL clones recognized HLA-B* 54:01 and -DRB1* 15:02 molecules, respectively, both of which were expressed in donor cells but not in patient cells. To test the effect of the CTL clones on engraftment, a colony forming assay using either HLA-B* 54:01 or -DRB1* 15:02-positive unrelated BMMNCs pre-cultured with the corresponding CTL clones was performed. Each of these CTL clones inhibited colony formation from unrelated BMMNCs sharing target HLA in a dose-dependent manner. These data suggest that the CTLs also impaired the cord blood engraftment. Furthermore, anti-HLA-B* 54:01 antibody was detected in cryopreserved pre-transplant patient serum, and in nested PCR assays specific for the HLA-B* 54:01-specific CTL clone’s uniquely rearranged T cell receptor V beta chain, PCR product was detected by amplification of cDNA from pre-transplant patient peripheral blood mononuclear cells. Thus, both HLA-B* 54:01-specific antibody and CTL clone developed in the patient prior to transplantation. The present data provide the first direct evidence showing that humoral and cellular immune responses were involved in the graft rejection. Of note is the recognition of the same mismatched HLA-B* 54:01 molecule by the DSA and CTL, suggesting that humoral and cellular immune processes acted together to mediate allograft rejection. Given the difficulty in detecting HLA-specific CTLs in pre-transplant patient blood in contrast to the easiness in screening for DSAs, the presence of DSA not only means a direct deleterious effect on donor cells but it may also reflect the presence of CTLs that causes allograft rejection. Further studies are warranted to clarify whether the present observation can be duplicated in other patients with DSA. We are conducting the study to clarify whether patients with anti-HLA antibodies have CTLs that recognize the same HLA molecules before transplantation. Disclosures: No relevant conflicts of interest to declare.

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Nakano, Toshiaki, Chao-Long Chen, and Shigeru Goto. "Nuclear Antigens and Auto/Alloantibody Responses: Friend or Foe in Transplant Immunology." Clinical and Developmental Immunology 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/267156.

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In addition to cellular immune responses, humoral immune responses, mediated by natural antibodies, autoantibodies, and alloantibodies, have increasingly been recognized as causes of organ transplant rejection. In our previous studies, we have demonstrated the induction of antinuclear antibodies against histone H1 and high-mobility group box 1 (HMGB1), in both experimental and clinical liver transplant tolerance. The active induction of antinuclear antibodies is usually an undesirable phenomenon, but it is often observed after liver transplantation. However, the release of nuclear antigens and its suppression by neutralizing antibodies are proposed to be important in the initiation and regulation of immune responses. In this review article, we summarize the current understanding of nuclear antigens and corresponding antinuclear regulatory antibodies (Abregs) on infection, injury, inflammation, transplant rejection, and tolerance induction and discuss the significance of nuclear antigens as diagnostic and therapeutic targets.

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Desmarets, Maxime, Chantel M. Cadwell, Kenneth R. Peterson, Renee Neades, and James C. Zimring. "Minor histocompatibility antigens on transfused leukoreduced units of red blood cells induce bone marrow transplant rejection in a mouse model." Blood 114, no. 11 (September 10, 2009): 2315–22. http://dx.doi.org/10.1182/blood-2009-04-214387.

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Abstract When successful, human leukocyte antigen (HLA)–matched bone marrow transplantation with reduced-intensity conditioning is a cure for several nonmalignant hematologic disorders that require chronic transfusion, such as sickle cell disease and aplastic anemia. However, there are unusually high bone marrow transplant (BMT) rejection rates in these patients. Rejection correlates with the number of transfusions before bone marrow transplantation, and it has been hypothesized that preimmunization to antigens on transfused blood may prime BMT rejection. Using a novel mouse model of red blood cell (RBC) transfusion and major histocompatibility complex–matched bone marrow transplantation, we report that transfusion of RBC products induced BMT rejection across minor histocompatibility antigen (mHA) barriers. It has been proposed that contaminating leukocytes are responsible for transfusion-induced BMT rejection; however, filter leukoreduction did not prevent rejection in the current studies. Moreover, we generated a novel transgenic mouse with RBC-specific expression of a model mHA and demonstrated that transfusion of RBCs induced a CD8+ T-cell response. Together, these data suggest that mHAs on RBCs themselves are capable of inducing BMT rejection. Cellular immunization to mHAs is neither monitored nor managed by current transfusion medicine practice; however, the current data suggest that mHAs on RBCs may represent an unappreciated and significant consequence of RBC transfusion.

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Hadaya, Karine, Sylvie Ferrari-Lacraz, Emiliano Giostra, Pietro Majno, Solange Moll, Laura Rubbia-Brandt, Nicola Marangon, et al. "Humoral and cellular rejection after combined liver-kidney transplantation in low immunologic risk recipients." Transplant International 22, no. 2 (October 13, 2008): 242–46. http://dx.doi.org/10.1111/j.1432-2277.2008.00775.x.

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Brain, J. G., H. Robertson, E. Thompson, E. H. Humphreys, A. Gardner, T. A. Booth, D. E. J. Jones, et al. "Biliary Epithelial Senescence and Plasticity in Acute Cellular Rejection." American Journal of Transplantation 13, no. 7 (June 10, 2013): 1688–702. http://dx.doi.org/10.1111/ajt.12271.

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Forbes, R. D., N. A. Parfrey, M. Gomersall, A. G. Darden, and R. D. Guttmann. "Dendritic cell-lymphoid cell aggregation and major histocompatibility antigen expression during rat cardiac allograft rejection." Journal of Experimental Medicine 164, no. 4 (October 1, 1986): 1239–58. http://dx.doi.org/10.1084/jem.164.4.1239.

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To determine the pattern of cellular expression of donor MHC class I and class II antigens during the course of rat cardiac allograft rejection, ACI cardiac allografts transplanted to BN recipients were examined from day 2 to day 6 using immunohistologic and immunoelectron microscopic methods. We used both monomorphic and donor-specific mouse anti-rat MHC class I and class II mAbs in this study. In normal ACI hearts, MHC class I reactivity was confined to the vascular endothelium and to interstitial cells. Ongoing rejection was characterized by an increased donor MHC class I staining intensity of microvascular endothelium and induction of donor class I surface reactivity on cardiac myofibers. Donor MHC class II reactivity was exclusively confined to interstitial dendritic cells (IDC) in both normal ACI hearts and in rejecting allografts, although rejection was associated with marked fluctuations in class II IDC frequency. An early numerical depression in class II IDC present in both allografts and syngeneic heart grafts was attributed to a direct effect of the transplantation procedure. By days 3-4, allografts showed an absolute overall increase in donor class II IDC frequency, which was associated with the presence of multiple localized high-density IDC-lymphocyte aggregates. The lymphocytes present in the focal areas were predominantly of the class II-reactive Th cell subpopulation. These aggregates may thus represent the in vivo homologue of dendritic cell-lymphocyte clustering, which has been shown to be required for primary class II allosensitization in the rat and mouse in vitro. During the late phase of rejection, there was a marked numerical fall in donor class II IDC, which correlated with extensive overall graft destruction. This study has shown that acute rat cardiac allograft rejection can occur in the absence of donor MHC class II expression by allograft vascular endothelium and cardiac myofibers. The IDC, which are believed to represent the principal class II alloantigen presenting cells in the rat heart, remain the sole class II-expressing cellular constituents of the graft throughout the course of rejection.

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Roden, Anja C., Dara L. Aisner, Timothy Craig Allen, Marie Christine Aubry, Roberto J. Barrios, Mary B. Beasley, Philip T. Cagle, et al. "Diagnosis of Acute Cellular Rejection and Antibody-Mediated Rejection on Lung Transplant Biopsies: A Perspective From Members of the Pulmonary Pathology Society." Archives of Pathology & Laboratory Medicine 141, no. 3 (November 7, 2016): 437–44. http://dx.doi.org/10.5858/arpa.2016-0459-sa.

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Context.— The diagnosis and grading of acute cellular and antibody-mediated rejection (AMR) in lung allograft biopsies is important because rejection can lead to acute graft dysfunction and/or failure and may contribute to chronic graft failure. While acute cellular rejection is well defined histologically, no reproducible specific features of AMR are currently identified. Therefore, a combination of clinical features, serology, histopathology, and immunologic findings is suggested for the diagnosis of AMR. Objective.— To describe the perspective of members of the Pulmonary Pathology Society (PPS) on the workup of lung allograft transbronchial biopsy and the diagnosis of acute cellular rejection and AMR in lung transplant. Data Sources.— Reports by the International Society for Heart and Lung Transplantation (ISHLT), experience of members of PPS who routinely review lung allograft biopsies, and search of literature database (PubMed). Conclusions.— Acute cellular rejection should be assessed and graded according to the 2007 working formulation of the ISHLT. As currently no specific features are known for AMR in lung allografts, the triple test (clinical allograft dysfunction, donor-specific antibodies, pathologic findings) should be used for its diagnosis. C4d staining might be performed when morphologic, clinical, and/or serologic features suggestive of AMR are identified.

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Franzese, O., A. Mascali, A. Capria, V. Castagnola, L. Paganizza, and N. Di Daniele. "Regulatory T Cells in the Immunodiagnosis and Outcome of Kidney Allograft Rejection." Clinical and Developmental Immunology 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/852395.

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Acute rejection (AR) is responsible for up to 12% of graft loss with the highest risk generally occurring during the first six months after transplantation. AR may be broadly classified into humoral as well as cellular rejection. Cellular rejection develops when donor alloantigens, presented by antigen-presenting cells (APCs) through class I or class II HLA molecules, activate the immune response against the allograft, resulting in activation of naive T cells that differentiate into subsets including cytotoxic CD8+and helper CD4+T cells type 1 (TH1) and TH2 cells or into cytoprotective immunoregulatory T cells (Tregs). The immune reaction directed against a renal allograft has been suggested to be characterized by two major components: a destructive one, mediated by CD4+helper and CD8+cytotoxic T cells, and a protective response, mediated by Tregs. The balance between these two opposite immune responses can significantly affect the graft survival. Many studies have been performed in order to define the role of Tregs either in the immunodiagnosis of transplant rejection or as predictor of the clinical outcome. However, information available from the literature shows a contradictory picture that deserves further investigation.

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Yamani, Mohamad H., Michael T. Kinter, Randall C. Starling, Belinda B. Willard, Norman B. Ratliff, Yang Yu, Daniel J. Cook, Patrick M. McCarthy, and James B. Young. "Increased β-Myosin Heavy Chain in Acute Cellular Rejection Following Human Heart Transplantation." American Journal of Transplantation 2, no. 4 (April 2002): 386–88. http://dx.doi.org/10.1034/j.1600-6143.2002.20416.x.

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Colvin, Gerald A., Eric S. Winer, and Peter J. Quesenberry. "HLA-Haploidentical Cellular Immunotherapy." Blood 110, no. 11 (November 16, 2007): 3075. http://dx.doi.org/10.1182/blood.v110.11.3075.3075.

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An immune-mediated anti-tumor response is the ultimate goal of allogeneic transplantation for relapsed, refractory malignancies. We developed a transplant protocol with less toxicity compared with standard allogeneic transplantation. We utilize multiple donor lymphocyte infusions after nonmyeloablative HLA-haploidentical stem cell transplantation for refractory disease. We have performed a total of 41 HLA-mismatched transplants with escalation of the CD3+ dose to 2×108 cells/kg using G-CSF primed product, with a conditioning regimen of 100cGy total body irradiation (TBI). Our phase I/II study had 26 with hematologic malignancies. This therapy results in loss of detectable macrochimerism. Despite this, 13 responses, six major, occurred outside of macrochimerism. We have observed a new infusion related clinical entity named haploimmunostorm (HIS), observed after infusion. This syndrome occurred in 26 out of 30 (87%) patients with a CD3+ dose more than 108 cells/kg. In the syndrome, a constellation of symptoms occurred, some with variable penetrance, in which hyperpyrexia and malaise were a constant feature occurring as early as 4 hrs after cell infusion (median of 14 hrs). A morbilliform rash was seen in 40% of patients. Biopsies revealed no evidence of hyperacute or acute GVHD. Diarrhea was present in a 20% of patients; biopsies taken also failed to show any evidence of GVHD. Transient elevations of liver enzymes occurred in 40% of the patients usually. Steroids were used successfully if the HIS syndrome lasted more than 72 hrs. We used a Bioplex machine and analyzed 17-separate cytokine levels serially in these patients beginning with pre-treatment levels. Cytokine level analysis showed a cluster of cytokines that had up to a 1100 fold level increase compared with baseline pretreatment cytokine levels with significant increases of at least 10 fold in IFN-g, IL-10, IL-13, IL-2, IL-5, IL-6, IL-7, IL-8, MCP-1, and MIP-1b. This syndrome appears to be immunologically based and represents neither hyperacute nor acute GVHD. This syndrome is different than an engraftment syndrome reported in some patients undergoing autologous transplant with a different cluster of cytokine elevation (IL-6, IL-8, IL-10, IFN-g, MCP-1, MIP-1b) compared with (IL-1, IL-2, IL-8, TNFa, IFNg) for engraftment syndrome Engraftment syndrome occurs at time of engraftment, opposed to HIS in which may be a rejection syndrome. HIS deviates from engraftment syndrome with absence of noncardiogenic edema, pulmonary infiltrates, renal insufficiency weight gain and encephalopathy. The skin and intestinal biopsy results are distinctly different than GVHD or engraftment syndrome. HIS may be critical to our observed tumor responses. The increased presence of MCP-1 and MIB-1b, which up-regulate NK cell function and recruitment, suggests that NK cells have some role in this syndrome and are possibly mediating tumor response, essentially breaking host tumor tolerance. In summary, we have observed a new clinical entity that was not previously seen and is a result of the donors having a relatively intact immune system at the time of cell infusion. TBI of 100cGy followed by HLA-haploidentical transplant is a biologically active therapy for refractory hematologic disease. The responses outside of chimerism are intriguing and may be related to marrow rejection and or a unique type of cytokine storm. These data further indicate that persistent donor chimerism may not be necessary for durable anti-tumor response. The rejection of donor derived cells, in concert with elevations of specific cytokines, may represent a novel therapeutic approach for hematological malignancies.

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Kirchhof, Nicole, Satoshi Shibata, Martin Wijkstrom, David M. Kulick, Christopher T. Salerno, Sue M. Clemmings, Yves Heremans, et al. "Reversal of diabetes in non-immunosuppressed rhesus macaques by intraportal porcine islet xenografts precedes acute cellular rejection." Xenotransplantation 11, no. 5 (September 2004): 396–407. http://dx.doi.org/10.1111/j.1399-3089.2004.00157.x.

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Luk, Josephine, Aaron M. Stoker, Emma Teixeiro, Keiichi Kuroki, Anna J. Schreiner, James P. Stannard, Robert Wissman, and James L. Cook. "Systematic Review of Osteochondral Allograft Transplant Immunology: How We Can Further Optimize Outcomes." Journal of Knee Surgery 34, no. 01 (January 2021): 030–38. http://dx.doi.org/10.1055/s-0040-1721670.

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AbstractDespite the growing success for osteochondral allograft (OCA) transplantation in treating large articular cartilage lesions in multiple joints, associated revision and failure rates are still higher than desired. While immunorejection responses have not been documented, the effects of the host's immune responses on OCA transplantation failures have not been thoroughly characterized. The objective of this study was to systematically review clinically relevant peer-reviewed evidence pertaining to the immunology of OCAs to elucidate theragnostic strategies for improving functional graft survival and outcomes for patients undergoing OCA transplantation. This systematic review of Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, MEDLINE, PubMed, and EMBASE suggests that host immune responses play key roles in incorporation and functional survival of OCA transplants. OCA rejection has not been reported; however, graft integration through creeping substitution is reliant on host immune responses. Prolonged inflammation, diminished osteogenic potential for healing and incorporation, and relative bioburden are mechanisms that may be influenced by the immune system and contribute to undesirable outcomes after OCA transplantation. Based on the safety and efficacy of OCA transplantation and its associated benefits to a large and growing patient population, basic, preclinical, and clinical osteoimmunological studies on OCA transplantation that comprehensively assess and correlate cellular, molecular, histologic, biomechanical, biomarkers, diagnostic imaging, arthroscopic, functional, and patient-reported outcome measures are of high interest and importance.

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Qian, Ying, and M. Reza Dana. "Molecular mechanisms of immunity in corneal allotransplantation and xenotransplantation." Expert Reviews in Molecular Medicine 3, no. 18 (July 16, 2001): 1–21. http://dx.doi.org/10.1017/s1462399401003246.

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Corneal allotransplantation is the most common and successful form of solid organ transplantation in humans. In uncomplicated cases, the two-year graft survival rate is over 90%. This extraordinary success can be attributed in part to various features of the normal cornea and anterior segment that together account for their ‘immune-privileged’ status. However, despite this success, a significant number of corneal grafts fail and immunological rejection remains by far the leading cause of graft failure. Studies on animal models of corneal transplantation have yielded a wealth of information on the molecular and cellular features of graft rejection, and have established that this process is mediated primarily by CD4+ T cells of the T helper 1 (Th1) phenotype. In addition, studies have elucidated that certain facets of allosensitisation differ between corneal and other solid organ transplants. On the basis of these findings, novel experimental strategies selectively targeting the afferent or efferent arms of corneal alloimmunity have provided promising results in preventing corneal allograft rejection in the laboratory. Finally, because of the global shortage of human donor corneas, there is currently renewed interest in the possibility of using corneas from other species for transplantation into human eyes (xenotransplantation). Preliminary studies on animal models of corneal xenotransplantation have documented both antibody-mediated and cell-mediated responses that might play important roles in the accelerated rejection observed in corneal xenotransplants. This review synthesises the principal concepts emerging from studies of the molecular mechanisms in corneal transplant immunology.

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Bayer, Allison L., Prabhakar Baliga, and Jennifer E. Woodward. "Differential effects of transferrin receptor blockade on the cellular mechanisms involved in graft rejection." Transplant Immunology 7, no. 3 (September 1999): 131–39. http://dx.doi.org/10.1016/s0966-3274(99)80032-x.

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Qian, Jin, Ricardo Moliterno, M. A. Donovan-Peluso, Kaihong Liu, Joe Suzow, Luis Valdivia, Pan Fan, and R. J. Duquesnoy. "Expression of stress proteins and lymphocyte reactivity in heterotopic cardiac allografts undergoing cellular rejection." Transplant Immunology 3, no. 2 (June 1995): 114–23. http://dx.doi.org/10.1016/0966-3274(95)80038-7.

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Tkhatl, L. K., T. V. Stavenchuk, E. D. Kosmachova, and I. A. Pashkova. "Criteria for diagnosis of humoral rejection using the method of 2D-speckle-tracking echocardiography." Russian Journal of Transplantology and Artificial Organs 21, no. 1 (May 18, 2019): 46–56. http://dx.doi.org/10.15825/1995-1191-2019-1-46-56.

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Aim: to identify predictors of humoral rejection at different stages using non-invasive methods of 2D-speckletracking echocardiography, to determine the correlation with immunological changes.Materials and methods. The study was conducted on the basis of Regional Clinic Hospital of Krasnodar from 2010 to 2017. The analysis of 181 heart recipients was performed. 5 groups were allocated due to the crisis of humoral rejection and the identified antibodies to donor leukocyte antigens (HLA antibodies): group 1 (n = 10) – DSA and humoral rejection, group 2 (n = 7), patients with non-DSA and humoral rejection, group 3 (n = 17) – patients with antibodies to HLA, no humoral rejection, group 4 (n = 11), humoral crisis of rejection, with no identified HLA antibodies, group 5 (n = 87) – patients do not have antibodies to HLA and signs of both humoral and cellular rejection according to EMB. Recipients were carried out endomyocardial biopsy, immunological study, 2D-speckle-tracking echocardiography, statistical methods.Results. The diagnostic criteria for a humoral rejection is greater than 1 degree are global peak systolic strain or strain rate of left ventricle (GLPSLV) – 9.94 ± 1.37% (the sensitivity was 86.2%, specificity – 90.4%); radial systolic strain (RadSLV) of 19.36 ± 3.66% (sensitivity was 75.8%, specificity – 84.5%); circumferential systolic strain (CiRSLV) – 17.83 ± 4.79% (sensitivity was 78.6%, specificity – 84.4%); the twisting of the left ventricle (twist) – 8.90 ± 1.85% (sensitivity – 66.7%, specificity – 94.2%), p < 0.001. When considering indicators GLPSLV and longitudinal peak strain of the right ventricle (GLPSRV) in the diagnosis of humoral rejection sensitivity increases to 91.9%, specificity increases to 94.6%, p < 0.001.Conclusion. GLPSLV has greater sensitivity at the stage of subclinical changes. It is more significantly reduced with increasing degree of rejection associated with episodes of rejection in comparison with other parameters and deformation mechanics. The interrelation between histological and immunological changes and impaired myocardial deformation. The proposed diagnostic algorithm will predict humoral rejection.

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Hall, B. M. "Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell." Journal of Experimental Medicine 161, no. 1 (January 1, 1985): 123–33. http://dx.doi.org/10.1084/jem.161.1.123.

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DA rats treated with hyperimmune anti-PVG serum and grafted with (DA X PVG)F1 heart grafts in which graft survival was prolonged for greater than 75 d were used to examine the cellular mechanisms that maintain the state of specific unresponsiveness found in these animals. The capacity of lymphocytes from these animals to effect or inhibit graft rejection on adoptive transfer to irradiated heart-grafted hosts was tested. Spleen cell populations and the T cell subpopulation separated from spleen cells in vitro failed to restore rejection of PVG heart grafts in irradiated DA recipients but restored third party Lew graft rejection. Whole spleen cells had the capacity to suppress the ability of normal DA LNC to cause graft rejection, but T cells from spleen only delayed the restoration of rejection. LNC and recirculating T cells from rats with enhanced grafts adoptively restored PVG rejection, however. These studies show that the state of specific unresponsiveness that follows the induction of passive enhancement is dependent in part upon active suppression, which is induced or mediated by T lymphocytes. The recirculating pool of lymphocytes in these animals is not depleted of specific alloreactive cells with the capacity to initiate and effect rejection. Thus, these animals' unresponsiveness is not like that found in transplantation tolerance induced in neonatal rats, but is, in part, due to a suppressor response that can inhibit normal alloreactive cells' capacity to initiate and effect rejection.

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Asaoka, Tadafumi, Shigeru Marubashi, Tomoaki Kato, Seigo Nishida, Panagiotis Tryphonopoulos, Akin Tekin, Edie Island, et al. "73-P: Preliminary Data of PCR-Based Custom Array for Acute Cellular Rejection After Liver Transplantation." Human Immunology 71 (September 2010): S66. http://dx.doi.org/10.1016/j.humimm.2010.06.123.

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Bonaccorsi-Riani, E., A. Pennycuick, M. C. Londoño, J. J. Lozano, C. Benítez, B. Sawitzki, M. Martínez-Picola, et al. "Molecular Characterization of Acute Cellular Rejection Occurring During Intentional Immunosuppression Withdrawal in Liver Transplantation." American Journal of Transplantation 16, no. 2 (October 30, 2015): 484–96. http://dx.doi.org/10.1111/ajt.13488.

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Gray, Derek W. R. "Comment on ''reversal of diabetes in non-immunosuppressed rhesus macaques by intraportal porcine islet xenografts precedes acute cellular rejection''." Xenotransplantation 11, no. 5 (September 2004): 394–95. http://dx.doi.org/10.1111/j.1399-3089.2004.00156.x.

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Zhang, Aiwen, Yuchu Sun, Katherine Zimmerman, Tana M. Zimmer, Julie Kemesky, Karen Seifarth, Jeffrey Allen, Mary Libby, and Ziad Zaky. "OR23 The impact of donor specific antibody in antibody mediated rejection and acute cellular rejection of kidney allografts after simultaneous liver-kidney transplantation." Human Immunology 80 (September 2019): 29–30. http://dx.doi.org/10.1016/j.humimm.2019.07.025.

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Pucci Molineris, Melisa, Virginia González Polo, Carolina Rumbo, Claudia Fuxman, Carlos Lowestein, Fabio Nachman, Martín Rumbo, Gabriel Gondolesi, and Dominik Meier. "Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis." Transplant Immunology 60 (June 2020): 101288. http://dx.doi.org/10.1016/j.trim.2020.101288.

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Xu, Hong, Paula M. Chilton, Yiming Huang, Carrie L. Schanie, Michael K. Tanner, Mariano Dy-Liacco, Lala-Rukh Hussain, and Suzanne T. Ildstad. "In the Absence of Preformed Antibody, Sensitized T Cells Mediate an Increased Barrier to Engraftment." Blood 106, no. 11 (November 16, 2005): 191. http://dx.doi.org/10.1182/blood.v106.11.191.191.

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Abstract Allosensitization resulting from transfusion therapy is a major challenge for the use of bone marrow transplantation to treat sickle cell disease. Prior exposure to foreign major histocompatibility complex (MHC) antigens through transfusion or transplantation is associated with an increased rate of solid organ graft rejection. Using a mouse model for sensitization, we recently found that humoral immunity plays a dominant role in sensitization to MHC alloantigens and concomitant graft rejection. The relative contribution of cellular versus humoral adaptive immune responses has not been fully characterized. In this study, we explored the role of host T cells in rejection of allografts by sensitized recipients using μ MT mice which are defective in producing mature B cells and antibody. Therefore, the barrier from preformed antibodies in sensitized normal mice would not exist in μ MT mice. μ MT (H-2b) mice were sensitized with BALB/c (H-2d) skin grafts. Although no anti-MHC alloantibody was detected in the μ MT mice after rejection, the skin grafts were rejected with a kinetic similar to normal controls (MST = 14.1 ± 1.2 days versus 13.6 ± 1.5 days). The prompt rejection of skin allografts by B cell deficient mice suggests that T cell activation and function are normal in vivo and that T cells alone are sufficient to reject allogeneic skin grafts. BMT was subsequently performed in presensitized μ MT mice 5 weeks after sensitization as well as in naïve μ MT mice. All naïve μ MT mice (n = 6) engrafted with 700 cGy TBI and 30 x 106 bone marrow cells, but none of the presensitized μ MT mice engrafted. Since humoral immunity is absent in sensitized μ MT mice, the increased barrier in these mice therefore must be mediated by the primed T cells. To further define the relative contribution of T cell subpopulations to alloresistance, we targeted these populations in vivo as preconditioning using monoclonal antibodies (mAb). Sensitized μ MT mice were treated with anti-α β-TCR, anti-CD8, anti-CD4 or anti-CD154 mAbs alone or in combination and 850 cGy of total body irradiation, then transplanted with untreated BALB/c donor bone marrow cells (Figure). Engraftment did not occur in the sensitized μ MT mice without mAb treatment, while nearly all animals engrafted with preconditioning with anti-α β-TCR alone, anti-CD8 plus anti-CD154, or anti-CD8 plus anti-CD4 (100%, 87.5%, and 100% respectively) and transplantation with 30 x 106 donor BM cells. Moreover, anti-α β-TCR preconditioning promoted engraftment in all sensitized μ MT mice with transplantation of as low as 15 x 106 BM cells. These data demonstrate that T cell mediated cellular immunity contributes to rejection in sensitized recipients, and that successful therapies to achieve allogeneic engraftment using nonmyeloablative conditioning in sensitized recipients will need to address both arms of the adaptive antigen-specific immune system: cellular and humoral. Figure Figure

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Colvin, Gerald A., David Berz, Muthalagu Ramanathan, Eric Winer, Loren D. Fast, Gerald Jay Elfenbein, and Peter J. Quesenberry. "Non-Engraftment Haploidentical Cellular Immunotherapy for Refractory Malignancies: Tumor Responses without Chimerism." Blood 112, no. 11 (November 16, 2008): 831. http://dx.doi.org/10.1182/blood.v112.11.831.831.

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Abstract Background: Allogeneic bone marrow transplantation (alloBMT) relies on immunosuppression to control graft-versus-host disease (GVHD) and allow successful engraftment; this happens at the expense of graft versus-tumor (GVT) activity. Advances in hematologic transplantation have prompted the development of effective, less toxic regimens attempting to balance graft-versus-host and GVT immunoreactions Conventional dogma holds that sustained chimerism/engraftment is necessary for prolonged responses. However, our previous study showed long-term response with transient chimerism, suggesting it was not necessary for therapeutic effect. In addition, Deyet al. showed anti-tumor responses with chimerism loss in 9/22 patients after non-myeloablative conditioning and alloBMT [Brit J Haem 128:2005]. In this phase I/II study, we determined recipient response rates with HLA-haploidentical donors, while infusing varying numbers of G-CSF primed cells. Methods: Forty-one patients with relapsed refractory cancers, significant co-morbidities, and ineligible for standard palliative or curative therapy, received 100-cGy total body irradiation (TBI) and infusion of G-CSF primed mobilized HLA-haploidentical cells. The product contained 1×106−2×108 CD3+ cells/kg. Twenty-nine patients received the highest dose. Results: The two highest CD3+ infusion cohorts caused a post-infusional cellular graft rejection syndrome. Symptoms resembled engraftment syndrome with cytokine elevations of IL-6, IL-10, IL-8, IFN-g, IL-5, IL-7, MCP-1 and MIP-1b. In the 26 patients with hematological malignancies there were 14-responses, 9-major. Two of six patients with lymphoma are presently free of disease at 74 and 80-months respectively; there were five durable complete-responses and four partial-responses in 13-patients with AML. All responses occurred without the presence of donor chimerism. Two patients who engrafted died; one due to GVHD and the other disease progression. We speculate that the cells responsible for the cytokine-storm, possibly tied to donor cell rejection, altered host tolerance to tumor and allowed for a host immune response against tumor. This theory is further supported in murine models showing that host anti-donor immune responses causing spontaneous or intentionally induced graft-rejection by recipient lymphocyte infusions, gave anti-tumor responses against recipient tumors [Blood 102:2003]. Conclusion: Non-engrafting Haploidentical transplant with minimal myeloablation (100cGy) is a therapeutic strategy appropriate for older patients with significant comorbidities, and it provides a virtual universal donor pool. Side-effects include well tolerated myelotoxicity and an immediate post-infusional steroid responsive immunologic syndrome. TBI of 100cGy followed by HLA-haploidentical transplant is a biologically active therapy for refractory hematologic disease. The responses outside of chimerism are intriguing and may be related to marrow rejection and or a unique type of cytokinestorm. These data further indicate that persistent donor chimerism may not be necessary for durable anti-tumor response. The rejection of donor-derived cells, in concert with elevations of specific cytokines, may represent a novel therapeutic approach for hematological malignancies.

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Neroev, V. V., N. V. Balatskaya, E. V. Chentsova, and Kh M. Shamkhalova. "Mechanisms of immune regulation and transplantation immunity in corneal transplants." Medical Immunology (Russia) 22, no. 1 (January 31, 2020): 61–76. http://dx.doi.org/10.15789/1563-0625-moi-1768.

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At the present time, corneal transplantation (keratoplasty) is one of the most frequent modes of solid tissue transplants in the world. Unlike other kinds of transplants, corneal grafting is often performed without tissue typing and systemic immunosuppression.High frequency of transparent corneal engraftment (up to 90% of cases) in the absence of risk factors is due to special immunoprivileged area in the anterior eye segment (functionally, a structural aggregation of the cornea and anterior chamber, AC) accomplished by local and systemic immunoregulatory mechanisms, i.e., phenomenon of immune deviation associated with anterior chamber of the eye (ACAID), components of the internal liquid medium, a watery moisture with immunosuppressive properties, e.g., IL-1ra, TSP-1,TGF-β2, regulatory complement proteins, α-MSH (alpha-melanocyte stimulating hormone), VIP (vasoactive intestinal peptide), indolamine 2,3-dioxygenase (IDO), calcitonin-gene-bound peptide (CGRP), somatostatin, etc.In addition to ACAID and liquid AC components, a contribution to the maintenance of immune privilege which is extremely important for a successful outcome of keratoplasty, is provided by other mechanisms, in particular, immunologically active membrane-associated molecules of corneal endothelium, i.e., PDL-1 (Programmed death ligand 1), and sVEGFR-1, sVEGFR-2, sVEGFR-3 involved in maintaining avascularity of the corneal tissue. Disturbances of the immune privilege of the cornea promotes activation of immune recognition with switching the effector mechanisms of transplantation immunity, thus leading to subsequent development of the tissue incompatibility reaction and clouding of transplanted cornea. Graft rejection can be localized in any of the corneal cell layers, including epithelium, stroma, and endothelium. Endothelial rejection causes the most severe affection of visual functions, due to the inability of local endothelial recovery, and water accumulation due to the endothelial dysfunction.Graft rejection is clinically characterized by edema and the presence of inflammatory cells, either circulating in the anterior chamber, or forming precipitates on the graft endothelial cells.A number of factors are associated with an increased risk of corneal graft rejection, including the degree of inflammation and/or vascularization of the transplant bed i.e., location of the donor cornea, repeated keratoplasty, allosensitization due to other cellular transplants, including bone marrow, blood transfusions, pregnancy, etc., as well as allergic and systemic diseases.This review article considers and systematizes the data from the literature concerning studies of the factors determining the immune privileged state of cornea, and the ACAID phenomenon, their role in development of allotolerance in corneal transplantation, highlights the main conditions required for triggering the tissue incompatibility reactions, discusses the mechanisms of allogeneic recognition and effector stage of the immune response, destruction of corneal allografts.

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Han, E. S., G. H. Na, H. J. Choi, Y. K. You, and D. G. Kim. "Effectiveness of Perioperative Immunologic Markers Monitoring for Predicting Early Acute Cellular Rejection After Living Donor Liver Transplantation." Transplantation Proceedings 51, no. 8 (October 2019): 2648–54. http://dx.doi.org/10.1016/j.transproceed.2019.03.077.

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Xu, Dan, Zaida Alipio, Jianchang Yang, Louis M. Fink, Wilson Xu, David C. Ward, and Yupo Ma. "Phenotypic Correction of Hemophilia a Using An Ips-Based Cellular Therapy." Blood 112, no. 11 (November 16, 2008): 514. http://dx.doi.org/10.1182/blood.v112.11.514.514.

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Abstract Hemophilia A, a sex-linked bleeding disorder, is caused by mutations within the genomic sequence of the Factor VIII (FVIII) gene. Mutations of FVIII lead to depleted or reduced protein production, and inefficient clotting. Because hemophilia A is caused by a single gene deficiency, several attempts at gene therapy have been made, including several phase I clinical trials. However, these have all failed for various reasons--including immune rejection. However, with the recent discovery of induced pluripotent stem (iPS) cells the immune rejection barrier can be circumvented. iPS cells can be generated from somatic cells by introducing the ectopic expression of three transcription factors Oct4, Sox2, Klf4 (Nakagawa et al., Nat Biotechnol.26: 101–106, 2008) To date, iPS cells have been indistinguishable from ES cells, and thus provide tremendous therapeutic potential. In this study, we differentiated iPS cells to endothelial and endothelial progenitor cells using the EB (embryonic bodies) differentiation method. iPS derived endothelial or endothelial progenitor cells express both endothelial or endothelial progenitor cell specific markers, such as CD31, and Flk1, as well as FVIII. These iPS-derived cells were directly injecting into the liver of irradiated hemophilia A model mice. Seven days after transplantation, hemophilia A and control mice were challenged by a tail-clip bleeding assay. Non-transplanted hemophilia A mice died within few hours, while transplanted mice survived for many weeks and more. Plasma FVIII expression in transplanted hemophilia A mice is significantly higher than in non-transplanted hemophilia mice and this elevated expression confers a correction on the hemophilia A phenotype in mice following a tail-clip. Our studies suggest that transplantation of iPS derived endothelial progenitor cells can rescue the phenotype of hemophilia in mouse models and thus potentially suitable for the future development of cell therapy of monogenetic disorders.

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Séveno, Céline, Flora Coulon, Fabienne Haspot, Emmanuel Mérieau, Karine Renaudin, Bernard Martinet, and Bernard Vanhove. "Induction of regulatory cells and control of cellular but not vascular rejection by costimulation blockade in hamster-to-rat heart xenotransplantation." Xenotransplantation 14, no. 1 (January 2007): 25–33. http://dx.doi.org/10.1111/j.1399-3089.2006.00361.x.

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Simonenko, M. A., T. M. Pervunina, P. A. Fedotov, Yu V. Sazonova, E. S. Vasichkina, V. E. Rubinchik, A. V. Berezina, et al. "THE EXPERIENCE OF PEDIATRIC HEART TRANSPLANTATION ON NORTH-WEST OF RUSSIAN FEDERATION." Russian Journal of Transplantology and Artificial Organs 20, no. 2 (June 27, 2018): 37–46. http://dx.doi.org/10.15825/1995-1191-2018-2-37-46.

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Aim:to estimate early and long-term outcomes in recipients under 18 years old who have been heart transplanted in Almazov National Medical Research Centre.Materials and methods. From April 2011 to September 2017 we performed 5 heart transplantations (HTx) in recipients under 18 years old (female) old) from adults donors. The median of age were 15 years (range 10–16 years), LVEF prior HTx – 17% (10–33%). Causes of heart failure were dilated cardiomyopathy (n = 2), non-compacted myocardium (n = 1), arrhythmogenic ventricular dysplasia (n = 1) and Ebstein’s anomaly (n = 1). They spent in HT waiting list 76 days (12–684 days). One patient underwent biventricular assist device Berlin Heart EXCOR implantation (days on support – 250) as a «bridge» to transplant. Due to coronary angiography (CAG) results 1 patient underwent HTx and CABG simultaneously. All recipients treated by triple-drug therapy (steroids, calcineurin inhibitors, mycophenolate mofetil), induction (thymoglobulin – n = 4, basiliximab – n = 1). We evaluated retrospectively laboratory-instrumental investigations and frequency of complications after HTx.Results.The median of survival after HT was 35,93 months (4,4–73,7 months), all of them are alive. Patients spent in ICU 12 days (4–18 days), but one – 18 days due to posterior reversible encephalopathy syndrome (PRES), tacrolimus was switched to cyclosporine. They required inotropic support during 3 days (3–8 days). In 1 yr after HT TTE results got to normal values, the same as VO2peak signiﬁ cantly improved. According to EMB (n = 48) results there were no clinical signs of rejection, acute cellular rejection (R2) was diagnosed in 12,5% cases. In long-term follow-up there was no signiﬁ cant post transplant complications and comorbidities.Conclusion.Pediatric heart transplantation is an effective treatment of terminal CHF. There was no signiﬁ cant clinical rejection under combined immunosuppressive regimens. All patients recovered and went back to normal life. Physical capacity improved in all recipients.

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Tarumi, K., A. Yagihashi, N. Watanabe, H. Kameshima, T. Yajima, and K. Hirata. "The Plasma FK506-Binding Protein 12 Level is Related to Acute Cellular Rejection in Small Bowel Transplantation." Immunopharmacology and Immunotoxicology 20, no. 2 (January 1998): 211–16. http://dx.doi.org/10.3109/08923979809038540.

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Gross, David-Alexandre, Marylène Leboeuf, Bernard Gjata, Olivier Danos, and Jean Davoust. "CD4+CD25+ regulatory T cells inhibit immune-mediated transgene rejection." Blood 102, no. 13 (December 15, 2003): 4326–28. http://dx.doi.org/10.1182/blood-2003-05-1454.

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AbstractLike cellular transplantation, gene therapy is often limited by immune rejection of the newly expressed antigen. In a model of gene transfer in muscle, delivery of the influenza hemagglutinin (HA) membrane protein by adeno-associated virus (AAV) is impaired by a strong immune response that leads to a rapid rejection of the transduced fibers. We show here that injection of HA-specific CD4+CD25+ T cells from T-cell receptor (TCR)-transgenic animals, concomitant with gene transfer, down-regulates the anti-HA cytotoxic and B-lymphocyte responses and enables persistent HA expression in muscle. This demonstrates for the first time that adoptive transfer of antigen-specific CD4+CD25+ regulatory T cells can be used to induce sustained transgene engraftment in solid tissues. (Blood. 2003;102:4326-4328)

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Pearson, Erik G., Jesse D. Vrecenak, Tricia R. Bhatti, William H. Peranteau, and Alan W. Flake. "Donor Specific Tolerance Of Renal Allografts Following Haploidentical In Utero Hematopoietic Cell Transplantation In The Canine Model." Blood 122, no. 21 (November 15, 2013): 2007. http://dx.doi.org/10.1182/blood.v122.21.2007.2007.

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Abstract Introduction In utero hematopoietic cell transplantation (IUHCT) can result in allogeneic mixed hematopoietic chimerism and associated donor specific tolerance (DST). We have reported a 1-2% donor chimerism threshold for consistent DST in the murine model as defined by the ability to enhance engraftment postnatally with a same donor minimal conditioning BMT, and have confirmed this finding in the canine model of IUHCT. Recently, we have optimized the canine model and achieved higher levels of chimerism (average>10%). As prenatal tolerance induction for postnatal organ transplantation is one of the clinical goals of IUHCT, we hypothesized that the presence of donor chimerism (>2.0%) after haploidentical IUHCT in the canine model would be sufficient to allow same donor renal transplants without immunosuppression. Method Stable mixed hematopoietic macrochimerism was documented by VNTR after haploidentical IUHCT performed at 40 days gestation using maternal donor BM cells in 4 pups (chimerism levels 3-38%). One positive control canine with no detectable chimerism following IUHCT also underwent haploidentical renal transplantation. Renal transplantation was performed from the maternal donor at ages between 12 and 18 months, and the pups were serially followed by ultrasound of the graft, blood chemistry and urinalysis post transplant. At 60 days an open biopsy of the allograft was taken and at 6 months a graft nephrectomy was performed for histologic analysis. Results Following transplantation, all recipients demonstrated blood flow to the renal cortex and all laboratory values were within normal ranges. At 60 days and 6 months 3 of the 4 recipients demonstrated a graft without evidence of acute or chronic rejection. The recipient with the lowest level of chimerism (3%) demonstrated evidence of mild interstitial nephritis (Banff class 1 rejection) following transplantation at the time of renal biopsy which increased in severity to severe interstitial fibrosis and moderate tubular atrophy (Banff class 3 rejection) at the time of graft nephrectomy. The positive control canine without detectable chimerism demonstrated clinical and histologic evidence of acute rejection within one week of transplantation. Conclusion Our results support the ability of IUHCT to induce DST for haploidentical organ transplantation, in a large animal model, without the need for immunosuppression. In agreement with previous studies in the murine model there appears to be a threshold level of donor chimerism required for associated DST. Although our numbers are not adequate to establish absolute thresholds of chimerism predictive of DST for organ transplantation, it appears to be slightly higher than the 1-2% threshold established for cellular transplantation. Disclosures: No relevant conflicts of interest to declare.

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Barnes, Eleanor J., Marwa M. Abdel-Rehim, Yiannis Goulis, Mona Abou Ragab, Susane Davies, Amar Dhillon, Brian Davidson, Keith Rolles, and Andrew Burroughs. "Applications and Limitations of Blood Eosinophilia for the Diagnosis of Acute Cellular Rejection in Liver Transplantation." American Journal of Transplantation 3, no. 4 (April 2003): 432–38. http://dx.doi.org/10.1034/j.1600-6143.2003.00083.x.

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Serinsoz, Ebru, Oliver Bock, Wilfried Gwinner, Anke Schwarz, Hermann Haller, Hans Kreipe, and Michael Mengel. "Local Complement C3 Expression is Upregulated in Humoral and Cellular Rejection of Renal Allografts." American Journal of Transplantation 5, no. 6 (June 2005): 1490–94. http://dx.doi.org/10.1111/j.1600-6143.2005.00873.x.

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Crespo-Leiro, Maria G., Alberto Veiga-Barreiro, Nieves Domenech, Maria J. Paniagua, Pablo Pinon, Margarita Gonzalez-Cuesta, Eduardo Vazquez-Martul, Consuelo Ramirez, Jose J. Cuenca, and Alfonso Castro-Beiras. "Humoral Heart Rejection (Severe Allograft Dysfunction with no Signs of Cellular Rejection or Ischemia): Incidence, Management, and the Value of C4d for Diagnosis." American Journal of Transplantation 5, no. 10 (October 2005): 2560–64. http://dx.doi.org/10.1111/j.1600-6143.2005.01039.x.

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Jiang, Qi, Yawei Ru, Yang Yu, Keqiu Li, Yaqing Jing, Jianhai Wang, and Guang Li. "iTRAQ-based quantitative proteomic analysis reveals potential early diagnostic markers in serum of acute cellular rejection after liver transplantation." Transplant Immunology 53 (April 2019): 7–12. http://dx.doi.org/10.1016/j.trim.2018.11.005.

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Journal articles on the topic 'Transplantation immunology; Cellular rejection'

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