Immunobiology of Cardiac Allograft and Xenograft Transplantation

Pediatric Cardiac Surgery Annual - Tập 4 - Trang 123-157 - 2001
Biagio A. Pietra1, Ronald G. Gill1
1From the Division of Cardiology, Department of Pediatrics, The Children's Hospital, Denver, and the Department of Medicine, Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO.

Tài liệu tham khảo

Mayer, 1990, Orthotopic heart transplantation for complex congenital heart disease, J Thorac Cardiovasc Surg, 99, 484, 10.1016/S0022-5223(19)36979-X Boucek, 1990, Cardiac transplantation in infancy: Donors and recipients. Loma Linda University Pediatric Heart Transplant Group, J Pediatr, 116, 171, 10.1016/S0022-3476(05)82870-7 Webber, 1994, Orthotopic heart transplantation in children with congenital heart disease, Ann Thorac Surg, 58, 1664, 10.1016/0003-4975(94)91655-1 Sigfusson, 1997, Long-term survivors of pediatric heart transplantation: A multicenter report of sixty-eight children who have survived longer than five years, J Pediatr, 130, 862, 10.1016/S0022-3476(97)70270-1 Hunt, 1991, Long-term results of cardiac transplantation, Ann Rev Med, 42, 437, 10.1146/annurev.me.42.020191.002253 Zinkernagel, 1974, Restriction of in vitro T cell-mediated cytotoxicity in lymphocytec choriomeningitis within a syngeneic or semiallogeneic system, Nature, 248, 701, 10.1038/248701a0 Bretscher, 1970, A theory of selfnonself discrimination, Science, 169, 1042, 10.1126/science.169.3950.1042 Lafferty, 1975, A new analysis of allogeneic interactions, Aust J Exp Biol Med Sci, 53, 27, 10.1038/icb.1975.3 Talmage, 1977, Activation of cytotoxic T cells by nonstimulating tumor cells and spleen cell factor(s), Proc Natl Acad Sci U S A, 74, 1610, 10.1073/pnas.74.10.4610 June, 1990, Role of the CD28 receptor in T-cell activation, Immunol Today, 11, 211, 10.1016/0167-5699(90)90085-N Chen, 1994, Molecular cloning and expression of early T cell costimulatory molecule-1 and its characterization as B7-2 molecule, J Immunol, 152, 4929, 10.4049/jimmunol.152.10.4929 Schwartz, 1992, Costimulation of T lymphocytes: The role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy, Cell, 71, 1065, 10.1016/S0092-8674(05)80055-8 Damle, 1992, Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes, J Immunol, 148, 1985, 10.4049/jimmunol.148.7.1985 Grewal, 1996, Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis, Science, 273, 1864, 10.1126/science.273.5283.1864 Watts, 1999, T cell co-stimulatory molecules other than CD28, Curr Opin Immunol, 11, 286, 10.1016/S0952-7915(99)80046-6 Lafferty, 1983, Immunobiology of tissue transplantation: A return to the passenger leukocyte concept, Ann Rev Immunol, 1, 143, 10.1146/annurev.iy.01.040183.001043 Larsen, 1996, Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways, Nature, 381, 434, 10.1038/381434a0 Mandelbrot, 1999, Expression of B7 molecules in recipient, not donor, mice determines the survival of cardiac allografts, J Immunol, 163, 3753, 10.4049/jimmunol.163.7.3753 Szot, 2000, Absence of host B7 expression is sufficient for long-term murine vascularized heart allograft survival, Transplantation, 69, 904, 10.1097/00007890-200003150-00040 Pietra, 2000, CD4 T cell-mediated cardiac allograft rejection requires donor but not host MHC class II, J Clin Invest, 106, 1003, 10.1172/JCI10467 Lafferty, 1969, Reactions of the graft-versus-host (GVH) type, Aust J Exp Biol Med Sci, 47, 17, 10.1038/icb.1969.3 McCune, 1988, The SLID-hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function, Science, 241, 1632, 10.1126/science.2971269 Kawamura, 1992, Chronic human skin graft rejection in severe combined immunodeficient mice engrafted with human PBL from an HLA-presensitized donor, Transplantation, 53, 659, 10.1097/00007890-199203000-00032 Rouleau, 1996, Antigen-specific cytotoxic T cells mediate human fetal pancreas allograft rejection in SLID-hu mice, J Immunol, 157, 5710, 10.4049/jimmunol.157.12.5710 Friedman, 1999, Human CD4+ T cells mediate rejection of porcine xenografts, J Immunol, 162, 5256, 10.4049/jimmunol.162.9.5256 Friedman, 1999, A critical role for human CD4+ T-cells in rejection of porcine islet cell xenografts, Diabetes, 48, 2340, 10.2337/diabetes.48.12.2340 Korngold, 1985, Surface markers of T cells causing lethal graft-vs-host disease to class I vs class II H-2 differences, J Immunol, 135, 3004, 10.4049/jimmunol.135.5.3004 Shoskes, 1994, Indirect presentation of MHC antigens in transplantation, Immunol Today, 15, 32, 10.1016/0167-5699(94)90023-X Swain, 1983, T cell subsets and the recognition of MHC class, Immunol Rev, 74, 129, 10.1111/j.1600-065X.1983.tb01087.x Bennett, 1997, Induction of a CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate CD4+ T cell help, J Exp Med, 186, 65, 10.1084/jem.186.1.65 Brossart, 1997, Presentation of exogenous protein antigens on major histocompatibility complex class I molecules by dendritic cells: Pathway of presentation and regulation by cytokines, Blood, 90, 1594, 10.1182/blood.V90.4.1594 Kurts, 1996, Constitutive class I-restricted exogenous presentation of self antigens in vivo, J Exp Med, 184, 923, 10.1084/jem.184.3.923 Kurts, 1997, CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity, J Exp Med, 186, 2057, 10.1084/jem.186.12.2057 Halloran, 1996, Molecular mechanisms of new immunosuppressants, Clin Transplant, 10, 118 Halloran, 1996, In vivo immunosuppressive mechanisms, J Heart Lung Transplant, 15, 959 Kenyon, 1999, Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD 154, Proc Natl Acad Sci U S A, 96, 8132, 10.1073/pnas.96.14.8132 Kirk, 1997, CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates, Proc Natl Acad Sci U S A, 94, 8789, 10.1073/pnas.94.16.8789 Elwood, 1998, Prolonged acceptance of concordant and discordant xenografts with combined CD40 and CD28 pathway blockade, Transplantation, 65, 1422, 10.1097/00007890-199806150-00002 Feng, 1999, Prolonged xenograft survival of islets infected with small doses of adenovirus expressing CTLA4Ig, Transplantation, 67, 1607, 10.1097/00007890-199906270-00016 Gordon, 1998, Prolonged survival of rat islet and skin xenografts in mice treated with donor splenocytes and anti-CD154 monoclonal antibody, Diabetes, 47, 1199, 10.2337/diab.47.8.1199 Lenschow, 1992, Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA41g, Science, 257, 789, 10.1126/science.1323143 Weber, 1997, CTLA4-Ig prolongs survival of microencapsulated neonatal porcine islet xenografts in diabetic NOD mice, Cell Transplant, 6, 505, 10.1016/S0963-6897(97)00045-6 Yin, 1995, CD4-positive suppressor cells block allotransplant rejection, J Immunol, 154, 6339, 10.4049/jimmunol.154.12.6339 Herbert, 1988, Strategies of monoclonal antibody therapy that induce permanent tolerance of organ transplants, Transplantation, 46, 128S, 10.1097/00007890-198808001-00024 Shizuru, 1990, Induction of donor specific unresponsiveness to cardiac allografts in rats by pretransplant anti-CD4 monoclonal antibody therapy, Transplantation, 50, 366, 10.1097/00007890-199009000-00002 Onodera, 1996, Induction of “infectious” tolerance to MHC-incompatible cardiac all, grafts in CD4 monoclonal antibodytreated sensitized rat recipients, J Immunol, 157, 1944, 10.4049/jimmunol.157.5.1944 Pearson, 1992, Induction of transplantation tolerance in adults using donor antigen and anti-CD4 monoclonal antibody, Transplantation, 54, 475, 10.1097/00007890-199209000-00018 Pearson, 1993, Anti-CD4 monoclonal antibody-induced allograft survival is associated with a defect in interleukin-2-dependent T-cell activation, Transplant Proc, 25, 786 Orosz, 1996, Prevention of murine cardiac allograft rejection and gallium nitrate, Comparison with anti-CD4 monoclonal antibody. Transplantation, 61, 783 Krieger, 1996, CD4+ but not CD8+ cells are essential for allorejection, J Exp Med, 184, 2013, 10.1084/jem.184.5.2013 Chen, 1992, Tolerance in the mouse to major histocompatibility complex-mismatched heart allografts, and to rat heart xenografts, using monoclonal antibodies to CD4 and CD8, Eur J Immunol, 22, 805, 10.1002/eji.1830220326 Pietra, 1999, CD4 T cells acutely reject cardiac allografts via direct donor recognition, Transplant Proc, 31, 92, 10.1016/S0041-1345(98)01452-3 Sayegh, 1998, The role of Tcell costimulatory activation pathways in transplant rejection, N Engl J Med, 338, 1813, 10.1056/NEJM199806183382506 Wecker, 1994, CD4+ T cells, without CD8+ or B lymphocytes, can reject xenogeneic skin grafts, Xenotransplantation, 1, 8, 10.1111/j.1399-3089.1994.tb00045.x Gill, 1994, CD4+ T cells are both necessary and sufficient for islet xenograft rejection, Transplant Proc, 26, 1203 VanBuskirk, 1996, Acute rejection of cardiac allografts by noncytolytic CD4(+) T cell populations, Transplantation, 62, 300, 10.1097/00007890-199607270-00026 Gill, 1993, T-cell-T-cell collaboration in allograft responses, Curr Opin Immunol, 5, 782, 10.1016/0952-7915(93)90137-H Auchincloss, 1993, The role of “indirect” recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice, Proc Natl Acad Sci U S A, 90, 3373, 10.1073/pnas.90.8.3373 Stepkowski, 1987, The role of class I and class II MHC antigens in the rejection of vascularized heart allografts in mice, Transplantation, 44, 753, 10.1097/00007890-198712000-00006 VanBuskirk, 1996, Transfusion of polarized TH2-like cell populations into SLID mouse cardiac allograft recipients results in acute allograft rejection, Transplantation, 62, 229, 10.1097/00007890-199607270-00014 Fangmann, 1992, T cell recognition of donor major histocompatibility complex class I peptides during allograft rejection, Eur J Immunol, 22, 1525, 10.1002/eji.1830220627 Benham, 1995, Indirect T cell allorecognition of donor antigens contributes to the rejection of vascularized kidney allografts, Transplantation, 59, 1028, 10.1097/00007890-199504150-00019 Chen, 1996, Mechanisms of indirect allorecognition in graft rejection, Class II MHC allope pt ide-specific T cell clones transfer delayed-type hypersensitivity responses in vivo. Transplantation, 62, 705 Gould, 1999, Direct and indirect recognition: The role of MHC antigens in graft rejection, Immunol Today, 20, 77, 10.1016/S0167-5699(98)01394-2 Campos, 1995, Survival of MHC-deficient mouse heterotopic cardiac allografts, Transplantation, 59, 187, 10.1097/00007890-199501000-00006 Markees, 1998, Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and CTLA4, J Clin Invest, 101, 2446, 10.1172/JCI2703 Hanabuchi, 1994, Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity, Proc Natl Acad Sci U S A, 91, 4930, 10.1073/pnas.91.11.4930 Kagi, 1994, Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity, Science, 265, 528, 10.1126/science.7518614 Ju, 1994, Participation of target Fas protein in apoptosis pathway induced by CD4+ Th 1 and CD8+ cytotoxic T cells, Proc Natl Acad Sci U S A, 91, 4185, 10.1073/pnas.91.10.4185 Stalder, 1994, Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity, J Immunol, 152, 1127, 10.4049/jimmunol.152.3.1127 Seino, 1996, Contribution of Fas ligand to cardiac allograft rejection, Intl Immunol, 8, 1347, 10.1093/intimm/8.9.1347 Larsen, 1995, Fas-mediated cytotoxicity. An immunoeffector or immunoregulatory pathway in T cell-mediated immune responses?, Transplantation, 60, 221, 10.1097/00007890-199508000-00002 Nickerson, 1997, Manipulation of cytokine networks in transplantation: False hope or realistic opportunity for tolerance?, Transplantation, 63, 489, 10.1097/00007890-199702270-00001 Tracey, 1993, Tumor necrosis factor, other cytokines and disease, Ann Rev Cell Biol, 9, 317, 10.1146/annurev.cb.09.110193.001533 Josien, 1998, Fas ligand, tumor necrosis factor-alpha expression, and apoptosis during allograft rejection and tolerance, Transplantation, 66, 887, 10.1097/00007890-199810150-00013 Imagawa, 1990, Anti-tumor necrosis factor antibody enhances allograft survival in rats, J Surg Res, 48, 345, 10.1016/0022-4804(90)90072-A Saleem, 1996, Acute rejection of vascularized heart allografts in the absence of IFNgamma, Transplantation, 62, 1908, 10.1097/00007890-199612270-00039 Weis, 1997, Cardiac allograft vasculopathy: A review, Circulation, 96, 2069, 10.1161/01.CIR.96.6.2069 Costanzo, 1998, Heart transplant coronary artery disease detected by coronary angiography: A multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database, J Heart Lung Transplant, 17, 744 Grattan, 1989, Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis, JAMA, 261, 3561, 10.1001/jama.1989.03420240075030 Billingham, 1992, Histopathology of graft coronary disease, J Heart Lung Transplant, 11, 538 Gao, 1988, Accelerated coronary vascular disease in the heart transplant patient: Coronary arteriographic findings, J Am Coll Cardiol, 12, 334, 10.1016/0735-1097(88)90402-0 Russell, 1997, Alloantibody- and T cell-mediated immunity in the pathogenesis of transplant arteriosclerosis: Lack of progression to sclerotic lesions in B cell-deficient mice, Transplantation, 64, 1531, 10.1097/00007890-199712150-00005 Vella, 1999, Cellular and humoral mechanisms of vascularized allograft rejection induced by indirect recognition of donor MHC allopeptides, Transplantation, 67, 1523, 10.1097/00007890-199906270-00005 Forbes, 1994, Evidence that recipient CD8+ T cell depletion does not alter development of chronic vascular rejection in a rat heart allograft model, Transplantation, 57, 1238, 10.1097/00007890-199404270-00017 Koglin, 2000, Attenuated cardiac allograft vasculopathy in mice with targeted deletion of the transcription factor STAT4, Circulation, 101, 1034, 10.1161/01.CIR.101.9.1034 Nielsen, 1993, Evidence for a primarily humoral rejection mechanism in concordant xenogeneic heart transplantation. A sequential immunohistological study in a hamster-to-rat model, APMIS, 101, 587, 10.1111/j.1699-0463.1993.tb00151.x Fryer, 1995, Beyond hyperacute rejection. Accelerated rejection in a discordant xenograft model by adoptive transfer of specific cell subsets, Transplantation, 59, 171, 10.1097/00007890-199501270-00003 Rose, 1991, Histopathology of hyperacute rejection of the heart: Experimental and clinical observations in allografts and xenografts, J Heart Lung Transplant, 10, 223 Rose, 1993, Antibody-mediated rejection following cardiac transplantation, Transpl Rev, 7, 140, 10.1016/S0955-470X(05)80013-8 Kirk, 1993, Ex vivo characterization of human antiporcine hyperacute cardiac rejection, Transplantation, 56, 785, 10.1097/00007890-199310000-00003 Auchincloss, 1988, Xenogeneic transplantation: A review, Transplantation, 46, 120, 10.1097/00007890-198807000-00001 Calne, 1970, Organ transplantation between widely disparate species, Transplant Proc, 2, 550 Platt, 1991, The barrier to xenotransplantation, Transplantation, 52, 937, 10.1097/00007890-199112000-00001 Platt, 1998, Acute vascular rejection, Xenotransplantation, 5, 169, 10.1111/j.1399-3089.1998.tb00024.x Artrip, 1997, Cardiac xenotransplantation, Curr Opin Cardiol, 12, 172, 10.1097/00001573-199703000-00013 Byrne, 1997, Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage, Transplantation, 63, 149, 10.1097/00007890-199701150-00027 Auchincloss, 1990, Xenografting: A review, Transpl Rev, 4, 14, 10.1016/S0955-470X(11)80002-9 Leventhal, 1993, The immunopathology of cardiac xenograft rejection in the guinea pig-to-rat model, Transplantation, 56, 1, 10.1097/00007890-199307000-00001 Pascher, 1997, Immunopathological observations after xenogeneic liver perfusions using donor pigs transgenic for human decay-accelerating factor, Transplantation, 64, 384, 10.1097/00007890-199708150-00002 Hamelmann, 1994, Immediate destruction of xenogeneic islets in a primate model, Transplantation, 58, 1109, 10.1097/00007890-199411000-00009 Alter, 1990, Cellular basis of the proliferative response of human T cells to mouse xenoantigens, J Exp Med, 171, 333, 10.1084/jem.171.1.333 Rocha, 1991, Peripheral selection of the T cell repertoire, Science, 251, 1225, 10.1126/science.1900951 Kalinke, 1990, Strong xenogeneic HLA response in transgenic mice after introducing an a3 domain into HLA B27, Nature, 348, 642, 10.1038/348642a0 Gustafsson, 1990, Structure of miniature swine class II DRB genes: Conservation of hypervariable amino acid residues between distantly related mammalian species, Proc Natl Acad Sci U S A, 87, 9798, 10.1073/pnas.87.24.9798 Collins, 1989, Species specificity of interleukin 2 binding to individual receptor components, Eur J Immunol, 19, 1517, 10.1002/eji.1830190828 Moses, 1992, Evidence that multiple defects in cellsurface molecule interactions across species differences are responsible for diminished xenogeneic T cell responses, Transplantation, 53, 203, 10.1097/00007890-199201000-00039 Vignali, 1992, Species-specific binding of CD4 to the b2 domain of major histocompatibility complex class II molecules, J Exp Med, 175, 925, 10.1084/jem.175.4.925 Woolnough, 1979, Cytotoxic and proliferative lymphocyte responses to allogeneic and xenogeneic antigens in vitro, Aust J Exp Biol Med Sci, 57, 467, 10.1038/icb.1979.48 von Hoegen, 1989, Equivalence of human and mouse CD4 in enhancing antigen responses by a mouse class II-restricted T cell hybridoma, J Exp Med, 170, 1879, 10.1084/jem.170.6.1879 Law, 1994, Human CD4 restores normal T cell development and function in mice deficient in murine CD4, J Exp Med, 179, 1233, 10.1084/jem.179.4.1233 Barzaga-Gilbert, 1992, Species specificity and augmentation of responses to class II major histocompatibility complex molecules in human CD4 transgenic mice, J Exp Med, 175, 1707, 10.1084/jem.175.6.1707 Clayton, 1989, Identification of residues affecting class II versus HIV-1 gp120 binding, Nature, 339, 548, 10.1038/339548a0 Irwin, 1989, Species-restricted interactions between CD8 and the a3 domain of class I influence the magnitude of the xenogeneic response, J Exp Med, 170, 1091, 10.1084/jem.170.4.1091 Lucas, 1990, The human anti-murine xenogeneic cytotoxic response I. Dependence on responder antigen-presenting cells, J Immunol, 144, 4548, 10.4049/jimmunol.144.12.4548 Greenstein, 1986, The role of T cell accessory molecules in the generation of class II-specific xenogeneic cytolytic T cells, J Immunol, 136, 2358, 10.4049/jimmunol.136.7.2358 Guerder, 1994, Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor a leads to autoimmunity in transgenic mice, Proc Natl Acad Sci U S A, 91, 5138, 10.1073/pnas.91.11.5138 Coulombe, 1996, Tissue immunogenicity: The role of MHC antigen and the lymphocyte costimulator B7-1, J Immunol, 157, 4790, 10.4049/jimmunol.157.11.4790 Yi, 1999, CD4+ cells play a major role in xenogeneic human anti-pig cytotoxicity through the Fas/Fas ligand lytic pathway, Transplantation, 67, 435, 10.1097/00007890-199902150-00017 Loudovaris, 1996, CD4+ T cell mediated destruction of xenografts within cell-impermeable membranes in the absence of CD8+ T cells and B cells, Transplantation, 61, 1678, 10.1097/00007890-199606270-00003 Rollins, 1994, Evidence that activation of human T cells by porcine endothelium involves direct recognition of porcine SLA and costimulation by porcine ligands for LFA-1 and CD2, Transplantation, 57, 1709, 10.1097/00007890-199457120-00004 Yamada, 1995, Direct and indirect recognition of pig class II antigens by human T cells, Transplant Proc, 27, 258 Shishido, 1997, Recognition of porcine major histocompatibility complex class I antigens by human CD8+ cytolytic T cell clones, Transplantation, 64, 340, 10.1097/00007890-199707270-00028 Xu, 1999, Allele-specific and peptide-dependent recognition of swine leukocyte antigen class I by human cytotoxic T-cell clones, Transplantation, 68, 473, 10.1097/00007890-199908270-00005 Bravery, 1995, Direct recognition of SLA- and HLA-like class II antigens on porcine endothelium by human T cells results in T cell activation and release of interleukin-2, Transplantation, 60, 1024, 10.1097/00007890-199511150-00025 Kievits, 1988, Recognition of xeno-(HLA, SLA) major histocompatibility complex antigens by mouse cytotoxic T cells is not H-2 restricted: A study with transgenic mice, Proc Nail Acad Sci U S A, 86, 617, 10.1073/pnas.86.2.617 Simon, 1998, Cross-species interaction of porcine and human integrins with their respective ligands: Implications for xenogeneic tolerance induction, Transplantation, 66, 385, 10.1097/00007890-199808150-00017 Herrlinger, 1996, Human T-cell activation is mediate predominantly by direct recognition of porcine SLA and involves accessory molecule interaction of ICAM1/LFA 1 and CD2/LFA3, Transplant Proc, 28, 650 Mueller, 1997, Humanized porcine VCAMspecific monoclonal antibodies with chimeric IgG2/G4 constant regions block human leukocyte binding to porcine endothelial cells, Mol Immunol, 34, 441, 10.1016/S0161-5890(97)00042-4 Dorling, 1996, Significant primary indirect human T-cell anti-pig xenoresponses observed using immature porcine dendritic cells and SLA-class II-negative endothelial cells, Transplant Proc, 28, 654 Gill, 1995, Immunobiology of cellular transplantation, Cell Transplant, 4, 361, 10.1016/0963-6897(95)00019-T Hao, 1987, Role of the L3T4+ T cell in allograft rejection, J Immunol, 139, 4022, 10.4049/jimmunol.139.12.4022 Scully, 1994, Mechanisms in CD4 antibody-mediated transplantation tolerance: kinetics of induction, antigen dependency and role of regulatory T cells, Eur J Immunol, 24, 2383, 10.1002/eji.1830241019 Shizuru, 1987, Islet allograft survival after a single course of treatment of recipient with antibody to L3T4, Science, 237, 278, 10.1126/science.2955518 Zelenika, 1998, Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: No requirement for CD8+ T cells or B cells, J Immunol, 161, 1868, 10.4049/jimmunol.161.4.1868 Auchincloss, 1990, Rejection of transgenic skin expressing a xeno-class I antigen is CD4-dependent and CD8-independent, Transplant Proc, 22, 1059 Kaufman, 1988, Use of anti-L3T4 and anti-Ia treatments for prolongation of xenogeneic islet transplants, Transplantation, 46, 210, 10.1097/00007890-198808000-00005 Krieger, 1997, Rat pancreatic islet and skin xenograft survival in CD4 and CD8 knockout mice, J Autoimmunity, 10, 309, 10.1006/jaut.1997.0126 Lacy, 1989, Effect of transplantation site and aL3T4 treatment on survival of rat, hamster, and rabbit islet xenografts in mice, Transplantation, 47, 761, 10.1097/00007890-198905000-00002 Mandel, 1992, The survival of xeno-, allo- and isografts in NOD mice and xenografts in other strains, after immunosuppression with anti-CD4 monoclonal antibody, Diabet Nutr Metab, 5, 91 Pierson, 1989, Xenogeneic skin graft rejection is especially dependent on CD4+ T cells, J Exper Med, 170, 991, 10.1084/jem.170.3.991 Wilson, 1989, Role of CD4+ T-lymphocytes in rejection by mice of fetal pig proislet xenografts, Diabetes, 38, 217, 10.2337/diab.38.1.S217 Wolf, 1995, Donor antigen-presenting cell-independent rejection of islet xenografts, Transplantation, 60, 1164, 10.1097/00007890-199511270-00018 Bennett, 1998, Help for cytotoxic-T-cell responses is mediated by CD40 signalling, Nature, 393, 474, 10.1038/30996 Ridge, 1998, A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell, Nature, 393, 474, 10.1038/30989 Schoenberger, 1998, T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions, Nature, 393, 480, 10.1038/31002 Gill, 1992, The role of direct and indirect antigen presentation in the response to islet xenografts, Transplant Proc, 24, 642 Wang, 1991, The role of CD4+ and CD8+ T cells in the destruction of islet grafts by spontaneously diabetic mice, Proc Natl Acad Sci U S A, 88, 527, 10.1073/pnas.88.2.527 Simeonovic, 1992, CD4+ Tcell depletion in mice facilitates induction of tolerance to pig proislet xenografts: A comparison of NOD and CBA/H recipient models, Diabet Nutr Metab, 5, 133 Desai, 1993, Islet allograft, islet xenograft, and skin allograft survival in CD8+ T lymphocytedeficient mice, Transplantation, 55, 718, 10.1097/00007890-199304000-00006 Desai, 1993, Pancreatic islet allograft and xenograft survival in CD8+ T-lymphocyte-deficient recipients, Transplant Proc, 25, 961 Gill, 1992, Rejection of pancreatic islet xenografts does not require CD8+ T-lymphocytes, Transplant Proc, 24, 2877 Markmann, 1992, Indefinite survival of MHC class Ideficient murine pancreatic islet allografts, Transplantation, 54, 1085, 10.1097/00007890-199212000-00025 Markmann, 1994, Genetically engineered grafts to study xenoimmunity: A role for indirect antigen presentation in the destruction of major histocompatibility complex antigen deficient xenografts, Surgery, 116, 242 Coulombe, 1999, Tolerance to antigen-presenting celldepleted islet allografts is CD4 T cell dependent, J Immunol, 162, 2503, 10.4049/jimmunol.162.5.2503 Benda, 1996, Xenograft rejection of porcine islet-like cell clusters in immunoglobulin- or Fc-receptor g-deficient mice, Transplantation, 62, 1207, 10.1097/00007890-199611150-00003 Chitilian, 1998, The strength of cell-mediated xenograft rejection in the mouse is due to the CD4+ indirect response, Xenotransplantation, 5, 93, 10.1111/j.1399-3089.1998.tb00014.x Chu, 1997, Xenogeneic but not allogeneic pancreatic islet graft survival in recipients lacking humoral immunity and major histocompatibility complex class II antigens, Transplant Proc, 29, 901, 10.1016/S0041-1345(96)00227-8 Obatake, 1999, T cells are necessary and critical for xenograft rejection in new concordant cardiac xenotransplant model, Transplantation, 67, 1480, 10.1097/00007890-199906150-00016 Lin, 1999, Rejection of hamster cardiac xenografts by rat CD4+ or CD8+ T cells, Transplant Proc, 31, 959, 10.1016/S0041-1345(98)01856-9 Murphy, 1996, T cell recognition of xenoMHC peptides during concordant xenograft rejection, Transplantation, 61, 1133, 10.1097/00007890-199604270-00001 Wolf, 1993, Xenoreactive T-cell lines initiate pancreatic islet graft destruction in vivo, Transplant Proc, 25, 440 Mombaerts, 1992, RAG-1-deficient mice have no mature B and T lymphocytes, Cell, 68, 869, 10.1016/0092-8674(92)90030-G Karlsson-Parra, 1996, Xenograft rejection of porcine islet-like cell clusters in normal and natural killer cell-depleted mice, Transplantation, 61, 1313, 10.1097/00007890-199605150-00005 Arakawa, 1994, Prolongation of heart xenograft survival in the NK-deficient rat, Transplant Proc, 26, 1266 Candinas, 1996, T cell independence of macrophage and natural killer cell infiltration, cytokine production, and endothelial activation during delayed xenograft rejection, Transplantation, 62, 1920, 10.1097/00007890-199612270-00042 Lin, 1999, Rejection of cardiac xenografts by CD4+ or CD8+ T cells, J Immunol, 162, 1206, 10.4049/jimmunol.162.2.1206 Lin, 1997, Natural killer cell- and macrophage-mediated rejection of concordant xenografts in the absence of T and B cell responses, J Immunol, 158, 5658, 10.4049/jimmunol.158.12.5658 Lin, 1997, Rejection of cardiac xenografts by NK cells and macrophages, Transplant Proc, 29, 2354, 10.1016/S0041-1345(97)00399-0 Sobel, 1994, Poly I:C induction of a-interferon in the diabetes-prone BB and normal Wistar rats. Dose-response relationships, Diabetes, 43, 518, 10.2337/diab.43.4.518 Lanier, 1998, NK cell receptors, Ann Rev Immunol, 16, 359, 10.1146/annurev.immunol.16.1.359 Inverardi, 1997, Human natural killer lymphocytes directly recognize evolutionarily conserved oligosaccharide ligands expressed by xenogeneic tissues, Transplantation, 63, 1318, 10.1097/00007890-199705150-00021 Blakely, 1994, Activation of intragraft endothelial and mononuclear cells during discordant xenograft rejection, Transplantation, 58, 1059, 10.1097/00007890-199411270-00001 Deng, 1997, NK cells, macrophages, and humoral immune responses are dominant in primary nonfunction of islet grafts in the dog-to-rat xenotransplant model, Transplant Proc, 29, 2062, 10.1016/S0041-1345(97)00232-7 Itescu, 1996, Circulating human mononuclear cells exhibit augmented lysis of pig endothelium after activation with interleukin 2, Transplantation, 62, 1927, 10.1097/00007890-199612270-00043 Goodman, 1996, Direct activation of porcine endothelial cells by human natural killer cells, Transplantation, 61, 763, 10.1097/00007890-199603150-00016 Donnelly, 1997, Human natural killer cells account for non-MHC class I-restricted cytolysis of porcine cells, Cell Immunol, 175, 171, 10.1006/cimm.1996.1053 Kirk, 1993, The human antiporcine cellular repertoire. In vitro studies of acquired and innate cellular responsiveness, Transplantation, 55, 924, 10.1097/00007890-199304000-00043 Seebach, 1997, HLA-Cw3 expression on porcine endothelial cells protects against xenogeneic cytotoxicity mediated by a subset of human NK cells, J Immunol, 159, 3655, 10.4049/jimmunol.159.7.3655 Smyth, 1999, Accessory function for NK1.1 + natural killer cells producing interferon-gamma in xenospecific cytotoxic T lymphocyte differentiation, Transplantation, 68, 840, 10.1097/00007890-199909270-00017 Wells, 1999, Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance, Nat Med, 5, 1303, 10.1038/15260 Li, 2000, The role of T cell apoptosis in transplantation tolerance, Curr Opin Immunol, 12, 522, 10.1016/S0952-7915(00)00133-3 Qin, 1993, “Infectious” transplantation tolerance, Science, 259, 974, 10.1126/science.8094901 Takeuchi, 1992, Heart allografts in murine systems. The differential activation of Th2-like effector cells in peripheral tolerance, Transplantation, 53, 1281, 10.1097/00007890-199206000-00023 Dallman, 1993, Cytokines and peripheral tolerance to alloantigen, Immunol Rev, 133, 5, 10.1111/j.1600-065X.1993.tb01507.x Lakkis, 1997, Blocking the CD28-B7 T cell costimulation pathway induces long term cardiac allograft acceptance in the absence of IL-4, J Immunol, 158, 24432448, 10.4049/jimmunol.158.5.2443 Brent, 2000, Tolerance and its clinical significance, World J Surg, 24, 787, 10.1007/s002680010126 Streilein, 1987, Mechanisms of neonatal transplantation tolerance, Transplant Proc, 19, 82 Streilein, 1991, Neonatal tolerance of H-2 alloantigens. Procuring graft acceptance the “old-fashioned” way, Transplantation, 52, 1, 10.1097/00007890-199107000-00001 McCullagh, 1990, Curtailment of autoimmunity following parabiosis with a normal partner, Immunology, 71, 595 Mohler, 1987, Tolerance to class II major histocompatibility complex molecules is maintained in the presence of endogenous, interleukin 2-producing, tolerogen-specific T lymphocytes, J Immunol, 139, 2211, 10.4049/jimmunol.139.7.2211 Billingham, 1956, Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance, Philos Trans R Soc Lond B Biol Sci, 239, 357, 10.1098/rstb.1956.0006 Ramseier, 1973, T cells in recognition of histocompatibility antigens, Nature, 246, 351, 10.1038/246351a0 Gruchalla, 1983, Analysis of neonatally induced tolerance of H-2 alloantigens III. Ease of abolition of tolerance of class I, but not class II, antigens with infusions of syngeneic immunocompetent cells, Transplantation, 36, 318, 10.1097/00007890-198309000-00017 Posselt, 1990, Induction of donor-specific unresponsiveness by intrathymic islet transplantation, Science, 249, 1293, 10.1126/science.2119056 Sayegh, 1994, Mechanisms of acquired thymic unresponsiveness to renal allografts. Thymic recognition of immunodominant allo-MHC peptides induces peripheral T cell anergy, Transplantation, 58, 125, 10.1097/00007890-199407270-00001 Chavin, 1993, Combined anti-CD2 and anti-CD3 receptor monoclonal antibodies induce donorspecific tolerance in a cardiac transplant model, J Immunol, 151, 7249, 10.4049/jimmunol.151.12.7249 Thomas, 1997, Preclinical studies of allograft tolerance in rhesus monkeys: A novel anti-CD3-immunotoxin given peritransplant with donor bone marrow induces operational tolerance to kidney allografts, Transplantation, 64, 124, 10.1097/00007890-199707150-00022 Lehmann, 1997, Anti-CD4 monoclonal antibody-induced allograft tolerance in rats despite persistence of donor-reactive T cells, Transplantation, 64, 1181, 10.1097/00007890-199710270-00017 Hall, 1998, AntiCD4 monoclonal antibody-induced tolerance to MHC-incompatible cardiac allografts maintained by CD4+ suppressor T cells that are not dependent upon IL-4, J Immunol, 161, 5147, 10.4049/jimmunol.161.10.5147 Mottram, 1993, Tolerance induction with antiCD8 monoclonal antibodies in the mouse heart transplant model, Transplant Proc, 25, 2935 Howland, 2000, The roles of CD28 and CD40 ligand in T cell activation and tolerance, J Immunol, 164, 4465, 10.4049/jimmunol.164.9.4465 Niimi, 1998, The role of the CD40 pathway in alloantigen-induced hyporesponsiveness in vivo, J Immunol, 161, 5331, 10.4049/jimmunol.161.10.5331 Lazarovits, 1992, Inhibition of alloreactivity in vitro by monoclonal antibodies directed against restricted isoforms of the leukocytecommon antigen (CD45), Transplantation, 54, 724, 10.1097/00007890-199210000-00030 Basadonna, 1998, Antibody-mediated targeting of CD45 isoforms: A novel immunotherapeutic strategy, Proc Natl Acad Sci USA, 95, 3821, 10.1073/pnas.95.7.3821 Nicolls, 2000, Anti-LFA-1 therapy induces longterm islet allograft acceptance in the absence of IFN-gamma or IL-4, J Immunol, 164, 3627, 10.4049/jimmunol.164.7.3627 Isobe, 1997, Assessment of tolerance induction to cardiac allograft by anti-ICAM-1 and Anti-LFA-1 monoclonal antibodies, J Heart Lung Transplant, 16, 1149 Isobe, 1996, Effects of exogenous IL-2 on tolerance induction by anti-ICAM-1 and anti-LFA-1 monoclonal antibodies, Transplant Proc, 28, 1045 Isobe, 1996, Acceptance of primary skin graft after treatment with anti-intercellular adhesion molecule-1 and anti-leukocyte function-associated antigen-1 monoclonal antibodies in mice, Transplantation, 62, 411, 10.1097/00007890-199608150-00019 Huet, 1989, CD44 contributes to T cell activation, J Immunol, 143, 798, 10.4049/jimmunol.143.3.798 Hourmant, 1994, Prevention of acute rejection episodes with an anti-interleukin 2 receptor monoclonal antibody. II. Results after a second kidney transplantation, Transplantation, 57, 204, 10.1097/00007890-199401001-00008 Orosz, 1996, Local cellular immunology of experimental transplant vascular sclerosis, Clin Transplant, 10, 100 Hao, 1992, Facilitation of specific tolerance induction in adult mice by RS-61443, Transplantation, 53, 590, 10.1097/00007890-199203000-00020 Li, 1998, Combined costimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment, Transplantation, 66, 1387, 10.1097/00007890-199811270-00021 Hall, 1985, Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. Mediation of specific suppression by T helper/inducer cells, J Exp Med, 162, 1683, 10.1084/jem.162.5.1683 Ildstad, 1984, Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts, Nature, 307, 168, 10.1038/307168a0 Deng, 1997, IL-10 and TGF-beta gene transfer to rodent islets: effect on xenogeneic islet graft survival in naive and B-cell-deficient mice, Transplant Proc, 29, 2207, 10.1016/S0041-1345(97)00299-6 Judge, 1998, Utility of adenoviral-mediated Fas ligand gene transfer to modulate islet allograft survival, Transplantation, 66, 426, 10.1097/00007890-199808270-00003 Gainer, 1997, Expression of CTLA4-Ig by biolistically transfected mouse islets promotes islet allograft survival, Transplantation, 63, 1017, 10.1097/00007890-199704150-00019 Dallman, 1987, Specific cytotoxic T cells are found in the nonrejected kidneys of blood-transfused rats, J Exp Med, 165, 566, 10.1084/jem.165.2.566 Miller, 1990, Tissuespecific expression of allogeneic class II MHC molecules induces neither tissue rejection nor clonal inactivation of alloreactive T cells, J Immunol, 144, 334, 10.4049/jimmunol.144.1.334 Wekerle, 1998, Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance, J Exp Med, 187, 2037, 10.1084/jem.187.12.2037 Parker, 1995, Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and anti-body to CD40 ligand, Proc Natl Acad Sci U S A, 92, 9560, 10.1073/pnas.92.21.9560 VanBuskirk, 2000, Human allograft acceptance is associated with immune regulation, J Clin Invest, 106, 145155, 10.1172/JCI9171 Kavelaars, 1996, Ontogency of the responses of human peripheral blood T cells to glucocorticoids, Brain Behavior Immun, 10, 288, 10.1006/brbi.1996.0025 Goldblatt, 1998, Immunisation and the maturation of infant immune responses, Dev Biol Stand, 95, 125 Schelonka, 1998, Neonatal immunology, Semin Perinatol, 22, 2, 10.1016/S0146-0005(98)80003-7 Vigano, 1999, Differential development of type 1 and type 2 cytokines and beta-chemokines in the ontogeny of healthy newborns, Biol Neonate, 75, 1, 10.1159/000014071 Schelonka, 1998, T cell receptor repertoire diversity and clonal expansion in human neonates, Pediatr Res, 43, 396, 10.1203/00006450-199803000-00015 Neubert, 1998, Evaluation of the age-dependent development of lymphocyte surface receptors in children, Life Sci, 62, 1099, 10.1016/S0024-3205(98)00033-2 Phocas, 1998, Soluble intercellular adhesion molecule-1 in newborn infants, Eur J Pediatr, 157, 153, 10.1007/s004310050788 Mosmann, 1991, Diversity of cytokine synthesis and function of mouse CD4+ T cells, Immunol Rev, 123, 209, 10.1111/j.1600-065X.1991.tb00612.x Delespesse, 1998, Maturation of human neonatal CD4+ and CD8+ T lymphocytes into Th1/Th2 effectors, Vaccine, 16, 1415, 10.1016/S0264-410X(98)00101-7 Lilic, 1997, Cytokine production differs in children and adults, Pediatr Res, 42, 237, 10.1203/00006450-199708000-00018 Wells, 1998, Neonatal thymectomy: Does it affect immune function?, J Thorac Cardiovasc Surg, 115, 1041, 10.1016/S0022-5223(98)70403-9 Yamada, 1999, The effect of thymectomy on tolerance induction and cardiac allograft vasculopathy in a miniature swine heart/kidney transplantation model, Transplantation, 68, 485, 10.1097/00007890-199908270-00007