Tolerance-inducing immunosuppressive strategies in clinical transplantation: An overview

Drugs

Volumn 68, Issue 15, 2008, Pages 2113-2130

  Golshayan, Dela ^a   Pascual, Manuel ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

Alemtuzumab, therapeutic use; Antithymocyte globulin, therapeutic use; Belatacept, therapeutic use; Research and development; Transplantation

Indexed keywords

ALEMTUZUMAB; AZATHIOPRINE; B7 ANTIGEN; BASILIXIMAB; BELATACEPT; CALCINEURIN INHIBITOR; CD28 ANTIGEN; CD40 ANTIGEN; CD40 LIGAND; CD40 LIGAND MONOCLONAL ANTIBODY; CD86 ANTIGEN; CELL ADHESION MOLECULE; CHEMOKINE; CYCLOPHILIN; CYCLOSPORIN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; DACLIZUMAB; FINGOLIMOD; FK 506 BINDING PROTEIN; INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 2 RECEPTOR ANTIBODY; MAMMALIAN TARGET OF RAPAMYCIN; MONOCLONAL ANTIBODY CD28; MONOCLONAL ANTIBODY CD3; OKT 3; RITUXIMAB; TACROLIMUS; THYMOCYTE ANTIBODY; UNINDEXED DRUG;

ACUTE GRAFT REJECTION; ACUTE KIDNEY FAILURE; ANEMIA; ANTIGEN RECOGNITION; AUTOIMMUNE THROMBOCYTOPENIA; BONE MARROW DEPRESSION; BRADYCARDIA; CYTOKINE RELEASE SYNDROME; DENDRITIC CELL; DIABETES MELLITUS; DRUG HYPERSENSITIVITY; GASTROINTESTINAL SYMPTOM; GINGIVA HYPERPLASIA; GRAFT REJECTION; HIRSUTISM; HUMAN; HYPERLIPIDEMIA; HYPERTENSION; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOPATHOLOGY; IMMUNOSUPPRESSIVE TREATMENT; LEUKOPENIA; LIVER TOXICITY; LUNG EDEMA; MEGALOCYTOSIS; NEPHROTOXICITY; NEUROTOXICITY; NEUTROPENIA; ORGAN TRANSPLANTATION; POSTOPERATIVE COMPLICATION; REGULATORY T LYMPHOCYTE; RETINA MACULA EDEMA; REVIEW; SERUM SICKNESS; SIGNAL TRANSDUCTION; THROMBOCYTOPENIA; THROMBOTIC THROMBOCYTOPENIC PURPURA; THYROID DISEASE; TREMOR;

ANIMALS; GRAFT REJECTION; HUMANS; IMMUNOSUPPRESSIVE AGENTS; LEUKOCYTES; LONG-TERM CARE; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; TRANSPLANTATION IMMUNOLOGY; TRANSPLANTATION TOLERANCE;

EID: 53549121186     PISSN: 00126667     EISSN: 00126667     Source Type: Journal    
DOI: 10.2165/00003495-200868150-00004     Document Type: Review

References (126)

1. Sayegh MH, Carpenter CB. Transplantation 50 years later: progress, challenges, and promises. N Engl J Med 2004; 351 (26): 2761-6
2. Hernandez-Fuentes MP, Lechler RI. Chronic graft loss: immunological and non-immunological factors. Contrib Nephrol 2005; 146: 54-64
3. Pascual M, Theruvath T, Kawai T, et al. Strategies to improve long-term outcomes after renal transplantation. N Engl J Med 2002; 346 (8): 580-90
4. Magee CC, Pascual M. Update in renal transplantation. Arch Intern Med 2004; 164: 1373-88
5. Billingham RE, Brent L, Medawar PB. Actively acquired tolerance of foreign cells. Nature 1953; 172: 603-6
6. Lanzavecchia A, Sallusto F. Regulation of T cell immunity by dendritic cells. Cell 2001; 106 (3): 263-6
7. Barratt-Boyes SM, Thomson AW. Dendritic cells: tools and targets for transplant tolerance. Am J Transplant 2005; 5 (12): 2807-13
8. Gould DS, Auchincloss Jr H. Direct and indirect recognition: the role of MHC antigens in graft rejection. Immunol Today 1999; 20: 77-82
9. Jiang S, Herrera O, Lechler RI. New spectrum of allorecognition pathways: implications for graft rejection and transplantation tolerance. Curr Opin Immunol 2004; 16: 550-7
10. Smyth LA, Herrera OB, Golshayan D, et al. A novel pathway of antigen presentation by dendritic and endothelial cells: implications for allorecognition and infectious diseases. Transplantation 2006; 82: S15-8
11. Hornick PI, Mason PD, Baker RJ, et al. Significant frequencies of T cells with indirect anti-donor specificity in heart graft recipients with chronic rejection. Circulation 2000; 101: 2405-10
12. Baker RJ, Hernandez-Fuentes MP, Brookes PA, et al. Loss of direct and maintenance of indirect alloresponses in renal allograft recipients: implications for the pathogenesis of chronic allograft nephropathy. J Immunol 2001; 167: 7199-206
13. Lee RS, Yamada K, Houser SL, et al. Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy. Proc Natl Acad Sci U S A 2001; 98 (6): 3276-81
14. Reznik SI, Jaramillo A, SivaSai KS, et al. Indirect allorecognition of mismatched donor HLA class II peptides in lung transplant recipients with bronchiolitis obliterans syndrome. Am J Transplant 2001; 1 (3): 228-35
15. Wise MP, Bemelman F, Cobbold SP, et al. Linked suppression of skin graft rejection can operate through indirect recognition. J Immunol 1998; 161: 5813-6
16. Yamada A, Chandraker A, Laufer TM, et al. Recipient MHC class II expression is required to achieve long-term survival of murine cardiac allografts after costimulatory blockade. J Immunol 2001; 167: 5522-6
17. Kahan BD. Cyclosporin. N Engl J Med 1989; 321: 1725-38
18. Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342: 605-12
19. Meier-Kriesche HU, Schold JD, Srinivas TR, et al. Lack of improvement in renal allograft survival despite a marked decrease in acute rejection rates over the most recent era. Am J Transplant 2004; 4: 378-83
20. Ashton-Chess J, Giral M, Brouard S, et al. Spontaneous operational tolerance after immunosuppressive drug withdrawal in clinical renal allotransplantation. Transplantation 2007; 84 (10): 1215-9
21. Starzl TE, Demetris AJ, Murase N, et al. Cell migration, chimerism, and graft acceptance. Lancet 1992; 339: 1579-82
22. Starzl TE. Immunosuppressive therapy and tolerance of organ allografts. N Engl J Med 2008; 358: 407-11
23. Alexander SI, Smith N, Hu M, et al. Chimerism and tolerance in a recipient of a deceased-donor liver transplant. N Engl J Med 2008; 358: 369-74
24. VanBuskirk AM, Burlingham WJ, Jankowska-Gan E, et al. Human allograft acceptance is associated with immune regulation. J Clin Invest 2000; 106: 145-55
25. Baeten D, Louis S, Braud C, et al. Phenotypically and functionally distinct CD8+ lymphocyte populations in long-term drug-free tolerance and chronic rejection in human kidney graft recipients. J Am Soc Nephrol 2006; 17: 294-304
26. Louis S, Braudeau C, Giral M, et al. Contrasting CD25hiCD4+T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance. Transplantation 2006; 81: 398-407
27. Hernandez-Fuentes MP, Warrens AN, Lechler RI. Immunologic monitoring. Immunol Rev 2003; 196: 247-64
28. Bluestone JA, Matthews JB, Krensky AM. The Immune Tolerance Network: the "Holy Grail" comes to the clinic. J Am Soc Nephrol 2000; 11: 2141-6
29. Goldman M, Wood K. European research on cell and organ transplantation: towards novel opportunities? Transplant Int 2007; 20 (12): 1016-9
30. Remuzzi G. Cellular basis of long-term transplant acceptance: pivotal role of intrathymic clonal deletion and thymic dependence of bone marrow microchimerism-associated tolerance. Am J Kidney Dis 1998; 31 (2): 197-212
31. Ildstad ST, Sachs DH. Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts. Nature 1984; 307 (5947): 168-70
32. Sykes M. Mixed chimerism and transplant tolerance. Immunity 2001; 14 (4): 417-24
33. Sharabi Y, Sachs DH. Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen. J Exp Med 1989; 169 (2): 493-502
34. Sykes M, Szot GL, Swenson KA, et al. Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning. Nat Med 1997; 3 (7): 783-7
35. Wekerle T, Kurtz J, Ito H, et al. Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment. Nat Med 2000; 6 (4): 464-9
36. Fuchimoto Y, Huang CA, Yamada K, et al. Mixed chimerism and tolerance without whole body irradiation in a large animal model. J Clin Invest 2000; 105 (12): 1779-89
37. Kawai T, Sogawa H, Boskovic S, et al. CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. Am J Transplant 2004; 4 (9): 1391-8
38. Sayegh MH, Fine NA, Smith JL, et al. Immunologic tolerance to renal allografts after bone marrow transplants from the same donors. Ann Intern Med 1991; 114 (11): 954-5
39. Spitzer TR, Delmonico F, Tolkoff-Rubin N, et al. Combined histocompatibility leukocyte antigen-matched donor bone marrow and renal transplantation for multiple myeloma with end stage renal disease: the induction of allograft tolerance through mixed lymphohematopoietic chimerism. Transplantation 1999; 68: 480-4
40. Buhler LH, Spitzer TR, Sykes M, et al. Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. Transplantation 2002; 74: 1405-9
41. Strober S, Benike C, Krishnaswamy S, et al. Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity. Transplantation 2000; 69: 1549-54
42. Millan MT, Shizuru JA, Hoffmann P, et al. Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation. Transplantation 2002; 73 (9): 1386-91
43. Fudaba Y, Spitzer TR, Shaffer J, et al. Myeloma responses and tolerance following combined kidney and nonmyeloablative marrow transplantation: in vivo and in vitro analyses. Am J Transplant 2006; 6 (9): 2121-33
44. Scandling JD, Busque S, Dejbakhsh-Jones S, et al. Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med 2008; 358 (4): 362-8
45. Kawai T, Cosimi AB, Spitzer TR, et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 2008; 358 (4): 353-61
46. Lechler RI, Garden OA, Turka LA. The complementary roles of deletion and regulation in transplantation tolerance. Nat Rev Immunol 2003; 3 (2): 147-58
47. Harding FA, McArthur JG, Gross JA, et al. CD28-mediated signalling co-stimulates murine T cells and prevent induction of anergy in T-cell clones. Nature 1992; 356: 607-9
48. Lechler RI, Chai JG, Marelli-Berg F, et al. The contributions of T-cell anergy to peripheral T-cell tolerance. Immunology 2001; 103: 262-9
49. Golshayan D, Buhler L, Lechler RI, et al. From current immunosuppressive strategies to clinical tolerance of allografts. Transplant Int 2007; 20: 12-24
50. Tan HP, Smaldone MC, Shapiro R. Immunosuppressive preconditioning or induction regimens: evidence to date. Drugs 2006; 66 (12): 1535-45
51. Elster EA, Hale DA, Mannon RB, et al. The road to tolerance: renal transplant tolerance induction in nonhuman primate studies and clinical trials. Transplant Immunol 2004; 13: 87-99
52. Contreras JL, Wang PX, Eckhoff DE, et al. Peritransplant tolerance induction with anti-CD3-immunotoxin: a matter of proinflammatory cytokine control. Transplantation 1998; 65: 1159-69
53. Kirk AD, Mannon RB, Kleiner DE, et al. Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin. Transplantation 2005; 80 (8): 1051-9
54. Brennan DC, Flavin K, Lowell JA, et al. A randomized, double-blinded comparison of thymoglobulin versus atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999; 67 (7): 1011-8
55. Waldmann H, Hale G. CAMPATH: from concept to clinic. Phil Trans R Soc B 2005; 360: 1707-11
56. Caillard S, Dharnidharka V, Agodoa L, et al. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation. 2005; 80 (9): 1233-43
57. Calne R, Friend P, Moffatt S, et al. Prope tolerance, perioperative campath 1H, and low-dose cyclosporin monotherapy in renal allograft recipients. Lancet 1998; 351 (9117): 1701-2
58. Torrealba JR, Fernandez LA, Kanmaz T, et al. Immunotoxin-treated Rhesus monkeys: a model for renal allograft chronic rejection. Transplantation 2003; 76 (3): 524-30
59. Thomas JM, Eckhoff DE, Contreras JL, et al. Durable donor-specific T and B-cell tolerance in rhesus macaques induced with peritransplantation anti-CD3 immunotoxin and deoxyspergualin: absence of chronic allograft nephropathy. Transplantation 2000; 69: 2497-503
60. Hirshberg B, Preston EH, Xu H, et al. Rabbit antithymocyte globulin induction and sirolimus monotherapy supports prolonged islet allograft function in a nonhuman primate islet transplantation model. Transplantation 2003; 76 (1): 55-60
61. Kirk AD, Hale DA, Mannon RB, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation 2003; 76 (1): 120-9
62. Shapiro R, Jordan ML, Basu A, et al. Kidney transplantation under a tolerogenic regimen of recipient pretreatment and low-dose postoperative immunosuppression with subsequent weaning. Ann Surg 2003; 238 (4): 520-5
63. Swanson SJ, Hale DA, Mannon RB, et al. Kidney transplantation with rabbit antithymocyte globulin induction and sirolimus monotherapy. Lancet 2002; 360 (9346): 1662-4
64. Barth RN, Janus CA, Lillesand CA, et al. Outcomes at three years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation. Transplant Int 2006; 19 (11): 885-92
65. Tan HP, Kaczorowski DJ, Basu A, et al. Living donor renal transplantation using alemtuzumab induction and tacrolimus monotherapy. Am J Transplant 2006; 6 (10): 2409-17
66. Golshayan D, Pascual M. Drug-minimization or tolerance-promoting strategies in human kidney transplantation: is Campath-1H the way to follow? Transplant Int 2006; 19 (11): 881-4
67. Pearl JP, Parris J, Hale DA, et al. Immunocompetent T-cells with a memory-like phenotype are the dominant cell type following antibody-mediated T-cell depletion. Am J Transplant 2005; 5 (3): 465-74
68. Wu Z, Bensinger SJ, Zhang J, et al. Homeostatic proliferation is a barrier to transplantation tolerance. Nat Med 2004; 10 (1): 87-92
69. Mason D. A very high level of cross-reactivity is an essential feature of the T-cell receptor. Immunol Today 1998; 19: 395-404
70. Pantenburg B, Heinzel F, Das L, et al. T cells primed by Leishmania major infection cross-react with alloantigens and alter the course of allograft rejection. J Immunol 2002; 169: 3686-93
71. Adams AB, Williams MA, Jones TR, et al. Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest 2003; 111: 1887-95
72. Lakkis FG, Sayegh MH. Memory T cells: a hurdle to immunologic tolerance. J Am Soc Nephrol 2003; 14 (9): 2402-10
73. Ciancio G, Burke GW, Gaynor JJ, et al. The use of Campath-1H as induction therapy in renal transplantation: preliminary results. Transplantation 2004; 78 (3): 426-33
74. Opelz G. Efficacy of rejection prophylaxis with OKT3 in renal transplantation. Collaborative Transplant Study. Transplantation 1995; 60 (11): 1220-4
75. Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nature Rev Immunol 2007; 7: 622-32
76. Becker YT, Samaniego-Picota M, Sollinger HW. The emerging role of rituximab in organ transplantation. Transplant Int 2006; 19 (8): 621-8
77. Sayegh M, Turka L. The role of T cell costimulatory activation pathways in transplant rejection. N Eng J Med 1998; 338: 1813-2
78. Larsen CP, Elwood ET, Alexander DZ, et al. Long-term acceptance of skin and cardiac allografts after blocking CD40 and CD28 pathways. Nature 1996; 381 (6581): 434-8
79. Larsen CP, Pearson TC. The CD40 pathway in allograft rejection, acceptance, and tolerance. Curr Opin Immunol 1997; 9: 641-7
80. Kirk AD, Burkly LC, Batty DS, et al. Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nat Med 1999; 5 (6): 686-93
81. Kawai T, Andrews D, Colvin RB, et al. Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand [letter]. Nat Med 2000; 6: 114
82. Adams AB, Shirasugi N, Jones TR, et al. Development of a chimeric anti-CD40 monoclonal antibody that synergizes with LEA29Y to prolong islet allograft survival. J Immunol 2005; 174 (1): 542-50
83. Alegre ML, Frauwirth KA, Thompson CB. T-cell regulation by CD28 and CTLA-4. Nat Rev Immunol 2001; 1: 220-8
84. Orabona C, Grohmann U, Belladonna ML, et al. CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat Immunol 2004; 5 (11): 1134-42
85. Kirk AD, Tadaki DK, Celniker A, et al. Induction therapy with monoclonal antibodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates. Transplantation 2001; 72 (3): 377-84
86. Birsan T, Hausen B, Higgins JP, et al. Treatment with humanized monoclonal antibodies against CD80 and CD86 combined with sirolimus prolongs renal allograft survival in cynomolgus monkeys. Transplantation 2003; 75 (12): 2106-13
87. Levisetti MG, Padrid PA, Szot GL, et al. Immunosuppressive effects of human CTLA-4 Ig in a non human primate model of allogeneic pancreatic islet transplantation. J Immunol 1997; 159 (11): 5187-92
88. Kirk AD, Harlan DM, Armstrong NN, et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in primates. Proc Natl Acad Sci U S A 1997; 94: 8789-94
89. Adams AB, Shirasugi N, Durham MM, et al. Calcineurin inhibitor-free CD28 blockade-based protocol protects allogeneic islets in nonhuman primates. Diabetes 2002; 51 (2): 265-70
90. Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J transplant 2005; 5: 443-53
91. Vincenti F, Larsen C, Durrbach A, et al. Costimulation blockade with belatacept in renal transplantation. Belatacept Study Group. N Engl J Med 2005; 353 (8): 770-81
92. Jones ND, Van Maurik A, Hara M, et al. CD40-CD40ligand-independent activation of CD8+ T cells can trigger allograft rejection. J Immunol 2000; 165 (2): 1111-8
93. Koyama I, Nadazdin O, Boskovic S, et al. Depletion of CD8 memory T cells for induction of tolerance of a previously transplanted kidney allograft. Am J Transplant 2007; 7 (5): 1055-61
94. Perez VL, Van Parijs L, Biuckians A, et al. Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity 1997; 6 (4): 411-7
95. Zheng XX, Markees TG, Hancock WW, et al. CTLA4 signals are required to optimally induce allograft tolerance with combined donor-specific transfusion and anti-CD154 monoclonal antibody treatment. J Immunol 1999; 162 (8): 4983-90
96. Tang Q, Henriksen KJ, Boden EK, et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 2003; 171 (7): 3348-52
97. Vanhove B, Laflamme G, Coulon F, et al. Selective blockade of CD28 and not CTLA-4 with a single-chain Fv-alpha1-antitrypsin fusion antibody. Blood 2003; 102 (2): 564-70
98. Haspot F, Villemain F, Laflamme G, et al. Differential effect of CD28 versus B7 blockade on direct pathway of allorecognition and self-restricted responses. Blood 2002; 99 (6): 2228-34
99. Vincenti F, de Andres A, Becker T, et al. Interleukin-2 receptor antagonist induction in modern immunosuppression regimens for renal transplant recipients. Transplant Int 2006; 19 (6): 446-57
100. Webster AC, Playford EG, Higgins G, et al. Interleukin 2 receptor antagonists for renal transplant recipients: a meta-analysis of randomized trials. Transplantation 2004; 77 (2): 166-76
101. Game DS, Hernandez-Fuentes MP, Lechler RI. Everolimus and basiliximab permit suppression by human CD4+CD25+ cells in vitro. Am J Transplant 2005; 5 (3): 454-64
102. Baan CC, van der Mast BJ, Klepper M, et al. Differential effect of calcineurin inhibitors, anti-CD25 antibodies and rapamycin on the induction of FOXP3 in human T cells. Transplantation 2005; 80 (1): 110-7
103. Brinkmann V, Cyster JG, Hla T. FTY720: sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 2004; 4 (7): 1019-25
104. Tedesco-Silva H, Mourad G, Kahan BD, et al. FTY720, a novel immunomodulator: efficacy and safety results from the first phase 2A study in de novo renal transplantation.Transplantation 2005; 79 (11): 1553-60
105. Hancock WW, Wang L, Ye Q, et al. Chemokines and their receptors as markers of allograft rejection and targets for immunosuppression. Curr Opin Immunol 2003; 15 (5): 479-86
106. Hourmant M, Bedrossian J, Durand D, et al. A randomized multicenter trial comparing leukocyte function-associated antigen-1 monoclonal antibody with rabbit antithymocyte globulin as induction treatment in first kidney transplantations. Transplantation 1996; 62 (11): 1565-70
107. Vincenti F, Mendez R, Pescovitz M, et al. A phase I/II randomized open-label multicenter trial of efalizumab, a humanized anti-CD11a, anti-LFA-1 in renal transplantation. Am J Transplant 2007; 7 (7): 1770-7
108. Wong W, Venetz JP, Tolkoff-Rubin N, et al. 2005 immunosuppressive strategies in kidney transplantation: which role for calcineurin inhibitors? Transplantation 2005; 80: 289-96
109. Mele TS, Halloran PF. The use of mycophenolate mofetil in transplant recipients. Immunopharmacology 2000; 47 (2-3): 215-45
110. Remuzzi G, Lesti M, Gotti E, et al. Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial. Lancet 2004; 364: 503-12
111. Remuzzi G, Cravedi P, Costantini M, et al. Mycophenolate mofetil versus azathioprine for prevention of chronic allograft dysfunction in renal transplantation: the MYSS follow-up randomized, controlled clinical trial. J Am Soc Nephrol 2007; 18 (6): 1973-85
112. Zheng XX, Sanchez-Fueyo A, Sho M, et al. Favourably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance. Immunity 2003; 19 (4): 503-14
113. Wells AD, Li XC, Li Y, et al. Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance. Nat Med 1999; 5 (11): 1303-7
114. Battaglia M, Stabilini A, Roncarolo MG. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 2005; 105 (12): 4743-8
115. Zeiser R, Nguyen VH, Beilhack A, et al. Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production. Blood 2006; 108 (1): 390-9
116. Segundo DS, Ruiz JC, Izquierdo M, et al. Calcineurin inhibitors, but not rapamycin, reduce percentages of CD4+CD25+-FOXP3+ regulatory T cells in renal transplant recipients. Transplantation 2006; 82 (4): 550-7
117. Bluestone JA, Thomson AW, Shevach EM, et al. What does the future hold for cell-based tolerogenic therapy? Nature Rev Immunol 2007; 7: 650-4
118. Sakaguchi S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004; 22: 531-62
119. Long E, Wood KJ. Understanding FOXP3: progress towards achieving transplantation tolerance. Transplantation 2007; 84 (4): 459-61
120. Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nature Rev Immunol 2003; 3: 199-210
121. Graca L, Cobbold SP, Waldmann H. Identification of regulatory T cells in tolerated allografts. J Exp Med 2002; 195 (12): 1641-6
122. Kang SM, Tang Q, Bluestone JA. CD4+CD25+ regulatory T cells in transplantation: progress, challenges and prospects. Am J Transplant 2007; 7 (6): 1457-63
123. Golshayan D, Jiang S, Tsang J, et al. In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood 2007; 109: 827-35
124. Morelli AE, Thomson AW. Tolerogenic dendritic cells and the quest for transplant tolerance. Nature Rev Immunol 2007; 7: 610-21
125. Jonuleit H, Schmitt E, Schuler G, et al. Induction of IL 10-producing, nonproliferating CD4+ T-cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000; 192: 1213-22
126. Lechler R, Ng WF, Steinman RM. Dendritic cells in transplantation: friend or foe? Immunity 2001; 14: 357-68