Targeting CD28 to prevent transplant rejection

Expert Opinion on Therapeutic Targets

Volumn 18, Issue 2, 2014, Pages 225-242

  Yeung, Melissa Y ^a   Najafian, Nader ^a,b   Sayegh, Mohamed H ^a,c  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b DEPARTMENT OF COLORECTAL SURGERY   (United States)

^c AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

Author keywords

Abatacept; Belatacept; CD28; Costimulatory molecules; Cytotoxic T lymphocyte antigen 4; Transplantation

Indexed keywords

B7 ANTIGEN; BELATACEPT; CD28 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4;

ARTICLE; AUTOIMMUNE DISEASE; DRUG TARGETING; GRAFT REJECTION; HUMAN; IMMUNOLOGICAL TOLERANCE; MELANOMA; NONHUMAN; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRANSPLANTATION;

ANIMALS; ANTIGENS, CD28; CTLA-4 ANTIGEN; GRAFT REJECTION; HUMANS; T-LYMPHOCYTES;

EID: 84892575278     PISSN: 14728222     EISSN: 17447631     Source Type: Journal    
DOI: 10.1517/14728222.2014.863875     Document Type: Article

References (164)

1. Li XC, Rothstein DM, Sayegh MH. Costimulatory pathways in transplantation: challenges and new developments. Immunol Rev 2009;229(1):271-93
2. Alegre ML, Najafian N. Costimulatory molecules as targets for the induction of transplantation tolerance. Curr Mol Med 2006;6(8):843-57
3. Hara T, Fu SM, Hansen JA. Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). J Exp Med 1985;161(6):1513-24
4. Hodi FS, O'Day SJ, McDermott DF, et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N Engl J Med 2010;363(8):711-23
5. Genovese MC, Becker J-C, Schiff M, et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor α inhibition. N Engl J Med 2005;353(11):1114-23
6. Mease P, Genovese MC, Gladstein G, et al. Abatacept in the treatment of patients with psoriatic arthritis: results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial. Arthritis Rheum 2011;63(4):939-48
7. Vincenti F, Larsen C, Durrbach A, et al. Costimulation blockade with belatacept in renal transplantation. N Engl J Med 2005;353(8):770-81
8. Lechler RI, Garden OA, Turka LA. The complementary roles of deletion and regulation in transplantation tolerance. Nat Rev Immunol 2003;3(2):147-58
9. Boenisch O, Sayegh MH, Najafian N. Negative T-cell costimulatory pathways: their role in regulating alloimmune responses. Curr Opin Organ Transplant 2008;13(4):373-8
10. Lenschow DJ, Walunas TL, Bluestone JA. CD28/B7 system of t cell costimulation. Annu Rev Immunol 1996;14(1):233-58
11. Hamann Dr, Baars PA, Rep MHG, et al. Phenotypic and functional separation of memory and effector human CD8+ T Cells. J Exp Med 1997;186(9):1407-18
12. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol 2005;23(1):515-48
13. Collins AV, Brodie DW, Gilbert RJC, et al. The interaction properties of costimulatory molecules revisited. Immunity 2002;17(2):201-10
14. Pentcheva-Hoang T, Egen JG, Wojnoonski K, Allison JP. B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity 2004;21:401-13
15. Bromley SK, Iaboni A, Davis SJ, et al. The immunological synapse and CD28-CD80 interactions. Nat Immunol 2001;2(12):1159-66
16. Bour-Jordan H, Esensten JH, Martinez-Llordella M, et al. Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/B7 family. Immunol Rev 2011;241(1):180-205
17. Appleman AJ, Berezovskaya A, Grass I, Boussiotis VA. CD28 costimulation mediates T cell expansion via IL-2-independent and IL-2-dependent regulation of cell cycle progression. J Immunol 2000;164(1):144-51
18. Rowell EA, Walsh MC, Wells AD. Opposing roles for the cyclin-dependent kinase inhibitor p27kip1 in the control of CD4+ T cell proliferation and effector function. J Immunol 2005;174(6):3359-68
19. Boonen GJJC, Van Dijk AMC, Verdonck LF, et al. CD28 induces cell cycle progression by IL-2-independent down-regulation of p27(kip1) expression in human peripheral T lymphocytes. Eur J Immunol 1999;29(3):789-98
20. Boise LH, Minn AJ, Noel PJ, et al. CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL. Immunity 1995;3(1):87-98
21. Frauwirth KA, Riley JL, Harris MH, et al. The CD28 signaling pathway regulates glucose metabolism. Immunity 2002;16(6):769-77
22. Kundig TM, Shahinian A, Kawai K, et al. Duration of TCR stimulation determines costimulatory requirement of T cells. Immunity 1996;5(1):41-52
23. Alegre ML, Noel PJ, Eisfelder BJ, et al. Regulation of surface and intracellular expression of CTLA4 on mouse T cells. J Immunol 1996;157(11):4762-70
24. Walunas TL, Bakker CY, Bluestone JA. CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med 1996;183(6):2541-50
25. Perez VL. Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity 1997;6:411-17
26. Tivol EA, Borriello F, Schweitzer AN, et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995;3(5):541-7
27. Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995;270(5238):985-8
28. Ueda H. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003;423:506-11
29. Marder BA, Schroppel B, Lin M, et al. The impact of costimulatory molecule gene polymorphisms on clinical outcomes in liver transplantation. Am J Transplant 2003;3(4):424-31
30. Kim HJ, Jeong KH, Lee SH, et al. Polymorphisms of the CTLA4 gene and kidney transplant rejection in Korean patients. Transpl Immunol 2010;24(1):40-4
31. Rudd CE. The reverse stop-signal model for CTLA4 function. Nat Rev Immunol 2008;8(2):153-60
32. Rudd CE, Taylor A, Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol Rev 2009;229(1):12-26
33. van der Merwe PÄ, Bodian DL, Daenke S, et al. CD80 (B7-1) Binds both CD28 and CTLA-4 with a low affinity and very fast kinetics. J Exp Med 1997;185(3):393-404
34. Walunas TL. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1994;1:405-13
35. Martin M, Schneider H, Azouz A, Rudd CE. Cytotoxic T lymphocyte antigen 4 and CD28 modulate cell surface raft expression in their regulation of T cell function. J Exp Med 2001;194:1675-81
36. Schneider H. Reversal of the TCR stop signal by CTLA-4. Science 2006;313:1972-5
37. Schneider H, Smith X, Liu H, et al. CTLA-4 expression disrupts ZAP-70 microcluster formation, T-cell/APC conjugation and calcium mobilization. Eur J Immunol 2007;38:40-7
38. Marengere LE. Regulation of T cell receptor signaling by tyrosine phosphatase SYP association with CTLA-4. Science 1996;272:1170-3
39. Schneider H. Cutting edge: CTLA-4 (CD152) differentially regulates mitogenactivated protein kinases (extracellular signal-regulated kinase and c-Jun Nterminal kinase) in CD4+ T cells from receptor/ligand-deficient mice. J Immunol 2002;169;3475-9
40. Parry RV, Chemnitz JM, Frauwirth KA, et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol Cell Biol 2005;25(21):9543-53
41. Bachmann MF, Kohler G, Ecabert B, et al. Cutting edge: Lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous. J Immunol 1999;163(3):1128-31
42. Bachmann MF, Gallimore A, Jones E, et al. Normal pathogen-specific immune responses mounted by CTLA-4-deficient T cells: a paradigm reconsidered. Eur J Immunol 2001;31(2):450-8
43. Bachmann MF, Waterhouse P, Speiser DE, et al. Normal responsiveness of CTLA-4-deficient anti-viral cytotoxic T cells. J Immunol 1998;160(1):95-100
44. Homann D, Dummer W, Wolfe T, et al. Lack of intrinsic CTLA-4 expression has minimal effect on regulation of antiviral T-ceIl immunity. J Virol 2006;80(1):270-80
45. Wang CJ, Kenefeck R, Wardzinski L, et al. Cutting edge: cell-Extrinsic immune regulation by CTLA-4 expressed on conventional T cells. J Immunol 2012;189(3):1118-22
46. Qureshi OS, Zheng Y, Nakamura K, et al. Trans-endocytosis of CD80 and CD86: a molecular basis for the cellextrinsic function of CTLA-4. Science 2011;332(6029):600-3
47. Grohmann U, Orabona C, Fallarino F, et al. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol 2002;3(11):1097-101
48. Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 2004;4(10):762-74
49. Butte MJ, Keir ME, Phamduy TB, et al. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 2007;27(1):111-22
50. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008;26:677-704
51. Yao S, Zhu Y, Zhu G, et al. B7-h2 is a costimulatory ligand for CD28 in human. Immunity 2011;34(5):729-40
52. Sharpe AH. Mechanisms of costimulation. Immunol Rev 2009;229(1):5-11
53. Tao X, Constant S, Jorritsma P, Bottomly K. Strength of TCR signal determines the costimulatory requirements for Th1 and Th2 CD4+ T cell differentiation. J Immunol 1997;159(12):5956-63
54. Boyton RJ, Altmann DM. Is selection for TCR affinity a factor in cytokine polarization? Trends Immunol 2002;23(11):526-9
55. Salomon B, Lenschow DJ, Rhee L, et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000;12(4):431-40
56. Lenschow DJ, Herold KC, Rhee L, et al. CD28/B7 Regulation of Th1 and Th2 Subsets in the Development of Autoimmune Diabetes. Immunity 1996;5(3):285-93
57. Rulifson IC, Sperling AI, Fields PE, et al. CD28 costimulation promotes the production of Th2 cytokines. J Immunol 1997;158(2):658-65
58. Rogers PR, Croft M. CD28, Ox-40, LFA-1, and CD4 modulation of Th1/Th2 differentiation is directly dependent on the dose of antigen. J Immunol 2000;164(6):2955-63
59. Jorritsma PJ, Brogdon JL, Bottomly K. Role of TCR-induced extracellular signalregulated kinase activation in the regulation of early IL-4 expression in naive CD4+ T cell1. J Immunol 2003;170(5):2427-34
60. Alegre ML, Shiels H, Thompson CB, Gajewski TF. Expression and function of CTLA-4 in Th1 and Th2 cells. J Immunol 1998;161(7):3347-56
61. Bour-Jordan H, Grogan JL, Tang Q, et al. CTLA-4 regulates the requirement for cytokine-induced signals in T(H) 2 lineage commitment. Nat Immunol 2003;4(2):182-8
62. Oosterwegel MA, Mandelbrot DA, Boyd SD, et al. The role of CTLA-4 in regulating Th2 differentiation. J Immunol 1999;163(5):2634-9
63. Zygmunt B, Veldhoen M. T helper cell differentiation more than just cytokines. Adv Immunol 2011;109:159-96
64. Park H, Li Z, Yang XO, et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 2005;6(11):1133-41
65. L, Ying H, Yang Qiao G, et al. Cutting edge: CTLA-4-B7 interaction suppresses Th17 cell differentiation. J Immunol 2010;185(3):1375-8
66. Bouguermouh S, Fortin G, Baba N, et al. CD28 co-stimulation down regulates Th17 development. PLoS One 2009;4(3):e5087
67. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, Xlinked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001;27(1):20-1
68. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003;4:330-6
69. 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
70. Yang J, Riella LV, Boenisch O, et al. Paradoxical functions of B7: CD28 costimulation in a MHC class IImismatched cardiac transplant model. Am J Transplant 2009;9(12):2837-44
71. Riella LV, Liu T, Yang J, et al. Deleterious Effect of CTLA4-Ig on a treg-dependent transplant model. Am J Transplant 2012;12(4):846-55
72. Zheng Y, Manzotti CN, Liu M, et al. CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells. J Immunol 2004;172(5):2778-84
73. Takahashi T, Tagami T, Yamazaki S, et al. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyteassociated antigen 4. J Exp Med 2000;192(2):303-10
74. Wing K, Onishi Y, Prieto-Martin P, et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 2008;322(5899):271-5
75. Vasu C, Prabhakar BS, Holterman MJ. Targeted CTLA-4 engagement induces CD4+CD25+CTLA-4high T regulatory cells with target (allo)antigen specificity. J Immunol 2004;173(4):2866-76
76. Fallarino F, Grohmann U, Hwang KW, et al. Modulation of tryptophan catabolism by regulatory T cells. Nat Immunol 2003;4(12):1206-12
77. Grohmann U, Orabona C, Fallarino F, et al. CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol 2002;3(11):1097-101
78. Schmidt EM, Wang CJ, Ryan GA, et al. CTLA-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity. J Immunol 2009;182(1):274-82
79. Onishi Y, Fehervari Z, Yamaguchi T, Sakaguchi S. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc Natl Acad Sci USA 2008;105(29):10113-18
80. Oderup C, Cederbom L, Makowska A, et al. Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression. Immunology 2006;118(2):240-9
81. Wing K, Yamaguchi T, Sakaguchi S. Cell-autonomous and-non-autonomous roles of CTLA-4 in immune regulation. Trends Immunol 2011;32(9):428-33
82. Dejean AS, Beisner DR, Ch'en IL, et al. Transcription factor Foxo3 controls the magnitude of T cell immune responses by modulating the function of dendritic cells. Nat Immunol 2009;10(5):504-13
83. Boesteanu AC, Katsikis PD. Memory T cells need CD28 costimulation to remember. Semin Immunol 2009;21(2):69-77
84. Busch DH, Pamer EG. T Cell Affinity Maturation by Selective Expansion during Infection. J Exp Med 1999;189(4):701-10
85. Savage PA, Boniface JJ, Davis MM. A Kinetic basis for T cell receptor repertoire selection during an immune response. Immunity 1999;10(4):485-92
86. Croft M, Bradley LM, Swain SL. Naive versus memory CD4 T cell response to antigen: memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J Immunol 1994;152(6):2675-85
87. Dubey C, Croft M, Swain SL. Naive and effector CD4 T cells differ in their requirements for T cell receptor versus costimulatory signals. J Immunol 1996;157(8):3280-9
88. Suresh M, Whitmire JK, Harrington LE, et al. Role of CD28-B7 interactions in generation and maintenance of CD8 T cell memory. J Immunol 2001;167(10):5565-73
89. Kim SK, Schluns KS, Lefrancois L. Induction and visualization of mucosal memory CD8 T cells following systemic virus infection. J Immunol 1999;163(8):4125-32
90. Borowski AB, Boesteanu AC, Mueller YM, et al. Memory CD8+ T cells require CD28 costimulation. J Immunol 2007;179(10):6494-503
91. Fuse S, Zhang W, Usherwood EJ. Control of memory CD8+ T cell differentiation by CD80/CD86-CD28 costimulation and restoration by IL-2 during the recall response. J Immunol 2008;180(2):1148-57
92. Fuse S, Tsai CY, Rommereim LM, et al. Differential requirements for CD80/86-CD28 costimulation in primary and memory CD4 T cell responses to vaccinia virus. Cell Immunol 2011;266(2):130-4
93. Ndejembi MP, Teijaro JM, Patke DS, et al. Control of memory CD4 T cell recall by the CD28/B7 costimulatory pathway. J Immunol 2006;177(11):7698-706
94. Yamada A, Kishimoto K, Dong VM, et al. CD28-independent costimulation of T cells in alloimmune responses. J Immunol 2001;167(1):140-6
95. Demirci G, Amanullah F, Kewalaramani R, et al. Critical role of OX40 in CD28 and CD154-independent rejection. J Immunol 2004;172(3):1691-8
96. Yamada A, Salama AD, Sho M, et al. CD70 signaling is critical for CD28-independent CD8+ T cell-mediated alloimmune responses in vivo. J Immunol 2005;174(3):1357-64
97. Kawai K, Shahinian A, Mak TW, Ohashi PS. Skin allograft rejection in CD28-deficient mice. Transplantation 1996;61(3):352-5
98. Szot GL, Zhou P, Sharpe AH, et al. Absence of host B7 expression is sufficient for long-term murine vascularized heart allograft survival. Transplantation 2000;69(5):904-10
99. Maier S, Tertilt C, Chambron N, et al. Inhibition of natural killer cells results in acceptance of cardiac allografts in CD28-/-mice. Nat Med 2001;7(5):557-62
100. Schenk S, Kish DD, He C, et al. Alloreactive T cell responses and acute rejection of single class II MHCTargeting disparate heart allografts are under strict regulation by CD4 +CD25+ T cells. J Immunol 2005;174(6):3741-8
101. Lo DJ, Anderson DJ, Weaver TA, et al. Belatacept and sirolimus prolong nonhuman primate renal allograft survival without a requirement for memory T cell depletion. Am J Transplant 2013;13(2):320-8
102. Bingaman AW, Farber DL, Memory T. Cells in transplantation: generation, function, and potential role in rejection. Am J Transplant 2004;4(6):846-52
103. Ford ML, Kirk AD, Larsen CP. Donor-reactive T-cell stimulation history and precursor frequency: barriers to tolerance induction. Transplantation 2009;87(9 Suppl):S69-74
104. Douek DC, McFarland RD, Keiser PH, et al. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998;396(6712):690-5
105. McFarland RD, Douek DC, Koup RA, Picker LJ. Identification of a human recent thymic emigrant phenotype. Proc Natl Acad Sci USA 2000;97(8):4215-20
106. Pitcher CJ, Hagen SI, Walker JM, et al. Development and homeostasis of T cell memory in rhesus macaque. J Immunol 2002;168(1):29-43
107. Heeger PS, Greenspan NS, Kuhlenschmidt S, et al. Pretransplant frequency of donor-specific, IFN-(gamma)-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes. J Immunol 1999;163(4):2267-75
108. Adams AB, Williams MA, Jones TR, et al. Heterologous immunity provides a potent barrier to transplantation tolerance. J Clin Invest 2003;111(12):1887-95
109. Goldrath AW, Bogatzki LY, Bevan MJ. Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J Exp Med 2000;192(4):557-64
110. Murali-Krishna K, Ahmed R. Cutting edge: naive T cells masquerading as memory cells. J Immunol 2000;165(4):1733-7
111. 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
112. Stapler D, Lee ED, Selvaraj SA, et al. Expansion of effector memory TCR V (beta)4+CD8+ T cells is associated with latent infection-mediated resistance to transplantation tolerance. J Immunol 2008;180(5):3190-200
113. Floyd TL, Koehn BH, Kitchens WH, et al. Limiting the amount and duration of antigen exposure during priming increases memory T cell requirement for costimulation during recall. J Immunol 2011;186(4):2033-41
114. Nadazdin O, Boskovic S, Murakami T, et al. Host alloreactive memory T cells influence tolerance to kidney allografts in nonhuman primates. Sci Transl Med 2011;3(86):86ra51-1
115. Kuchroo VK, Prabhu Das M, Brown JA, et al. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1995;80(5):707-18
116. Lenschow DJ, Ho SC, Sattar H, et al. Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse. J Exp Med 1995;181(3):1145-55
117. Lenschow DJ, Zeng Y, Hathcock KS, et al. Inhibition of transplant rejection following treatment with anti-B7-2 and anti-B7-1 antibodies. Transplantation 1995;60(10):1171-8
118. Pearson TC, Alexander DZ, Corbascio M, et al. Analysis of the B7 costimulatory pathway in allograft rejection. Transplantation 1997;63(10):1463-9
119. 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
120. Tsai MK, Ho HN, Chien HF, et al. The role of b7 ligands (cd80 and cd86) in cd152-mediated allograft tolerance: a crosscheck hypothesis. Transplantation 2004;77(1):48-54
121. Haanstra KG, Ringers J, Sick EA, et al. Prevention of kidney allograft rejection using anti-CD40 and anti-CD86 in primates. Transplantation 2003;75(5):637-43
122. Peach RJ, Bajorath J, Brady W, et al. Complementarity determining region 1 (CDR1)-and CDR3-analogous regions in CTLA-4 and CD28 determine the binding to B7-1. J Exp Med 1994;180(6):2049-58
123. 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
124. Dengler TJ, Szabo G, Sido B, et al. Prolonged allograft survival but no tolerance induction by modulating CD28 antibody JJ319 after highresponder rat heart transplantation. Transplantation 1999;67(3):392-8
125. Dong VM, Yuan X, Coito AJ, et al. Mechanisms of targeting CD28 by a signaling monoclonal antibody in acute and chronic allograft rejection. Transplantation 2002;73(8):1310-17
126. Hunig T, Dennehy K. CD28 superagonists: mode of action and therapeutic potential. Immunol Lett 2005;100(1):21-8
127. Beyersdorf N, Gaupp S, Balbach K, et al. Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis. J Exp Med 2005;202(3):445-55
128. Beyersdorf N, Hanke T, Kerkau T, Hunig T. Superagonistic anti-CD28 antibodies: potent activators of regulatory T cells for the therapy of autoimmune diseases. Ann Rheum Dis 2005 Nov;64(Suppl 4):iv91-5
129. Beyersdorf N, Hanke T, Kerkau T, Hunig T. CD28 superagonists put a break on autoimmunity by preferentially activating CD4+CD25+ regulatory T cells. Autoimmun Rev 2006;5(1):40-5
130. Suntharalingam G, Perry MR, Ward S, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 2006;355(10):1018-28
131. Eastwood D, Findlay L, Poole S, et al. Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells. Br J Pharmacol 2010;161(3):512-26
132. Stebbings R, Findlay L, Edwards C, et al. "Cytokine storm" in the Phase I trial of monoclonal antibody TGN1412: better understanding the causes to improve preclinical testing of immunotherapeutics. J Immunol 2007;179(5):3325-31
133. Vanhove B, Laflamme Gv, Coulon F, et al. Selective blockade of CD28 and not CTLA-4 with a single-chain Fv Ä쌱1-antitrypsin fusion antibody. Blood 2003;2003:102(2):564-70
134. Luhder F, Huang Y, Dennehy KM, et al. Topological requirements and signaling properties of T cell-activating, anti-CD28 antibody superagonists. J Exp Med 2003;197(8):955-66
135. Poirier N, Azimzadeh AM, Zhang T, et al. Inducing CTLA-4-dependent immune regulation by selective CD28 blockade promotes regulatory T cells in organ transplantation. Sci Transl Med 2010;2(17):17ra10
136. Vincenti F, Dritselis A, Kirkpatrick P. Belatacept. Nat Rev Drug Dis 2011;10(9):655-6
137. Kremer JM, Westhovens R, Leon M, et al. Treatment of rheumatoid arthritis by selective inhibition of T-Cell activation with fusion protein CTLA4Ig. N Engl J Med 2003;349(20):1907-15
138. Kirk AD, Harlan DM, Armstrong NN, et al. CTLA4-Ig and anti-CD40 ligand prevent renal allograft rejection in Äâprimates. Proc Natl Acad Sci USA 1997;94(16):8789-94
139. Levisetti MG, Padrid PA, Szot GL, et al. Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation. J Immunol (Baltimore, Md : 1950) 1997;159(11):5187-91
140. Sayegh MH, Akalin E, Hancock WW, et al. CD28-B7 blockade after alloantigenic challenge in vivo inhibits Th1 cytokines but spares Th2. J Exp Med 1995;181(5):1869-74
141. Ronchese F, Hausmann B, Hubele S, Lane P. Mice transgenic for a soluble form of murine CTLA-4 show enhanced expansion of antigen-specific CD4+ T cells and defective antibody production in vivo. J Exp Med 1994:179(3):809-17
142. Khoury SJ, Akalin E, Chandraker A, et al. CD28-B7 costimulatory blockade by CTLA4Ig prevents actively induced experimental autoimmune encephalomyelitis and inhibits Th1 but spares Th2 cytokines in the central nervous system. J Immunol 1995;155(10):4521-4
143. 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(3):443-53
144. Tan P, Anasetti C, Hansen JA, et al. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1. J Exp Med 1993:177(1):165-73
145. 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
146. Judge TA. The role of CD80, CD86, and CTLA4 in alloimmune responses and the induction of long-term allograft survival. J Immunol 1999;162:1947-51
147. Turka LA. T-cell activation by the CD28 ligand B7 is required for cardiac allograft rejection in vivo. Proc Natl Acad Sci USA 1992;89:11102-5
148. Li W. Costimulation blockade promotes the apoptotic death of graft-infiltrating T cells and prolongs survival of hepatic allografts from FLT3L-treated donors. Transplantation 2001;78:1423-32
149. Lenschow DJ. Long-term survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig. Science 1992;257:789-92
150. Pearson TC, Alexander DZ, Hendrix R, et al. CTLA4-Ig plus bone marrow induces long-term allograft survival and donor-specific unresponsiveness in the murine model: evidence for hematopoietic chimerism1. Transplantation 1996;61(7):997-1004
151. Williams MA, Trambley J, Ha J, et al. Genetic characterization of strain differences in the ability to mediate CD40/CD28-independent rejection of skin allografts. J Immunol 2000;165:12):757
152. Zheng XX, Sanchez-Fueyo A, Sho M, et al. Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance. Immunity 2003;19(4):503-14
153. Mellor AL, Baban B, Chandler P, et al. Cutting edge: induced indoleamine 2,3 dioxygenase expression in dendritic cell subsets suppresses T cell clonal expansion. J Immunol 2003;171(4):1652-5
154. Sucher R, Fischler K, Oberhuber R, et al. IDO and regulatory T cell support are critical for cytotoxic T lymphocyteassociated Ag-4 Ig-mediated long-term solid organ allograft survival. J Immunol 2012;188(1):37-46
155. Li Y, Li XC, Zheng XX, et al. Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat Med 1999;5(11):1298-302
156. Xu H, Montgomery SP, Preston EH, et al. Studies investigating pretransplant donor-specific blood transfusion, rapamycin, and the CD154-specific antibody IDEC-131 in a nonhuman primate model of skin allotransplantation. J Immunol 2003;170(1):2776-82
157. D'Addio F, Yuan X, Habicht A, et al. A novel clinically relevant approach to tip the balance toward regulation in stringent transplant model. Transplantation 2010;90(1):260-9
158. 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
159. Vincenti F, Larsen CP, Alberu J, et al. Three-year outcomes from BENEFIT, a randomized, active-controlled, parallelgroup study in adult kidney transplant recipients. Am J Transplant 2012;12(1):210-17
160. Medina Pestana JO, Grinyo JM, Vanrenterghem Y, et al. Three-Year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys. Am J Transplant 2012;12(3):630-9
161. Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant 2010;10(3):535-46
162. Bluestone JA, Liu W, Yabu JM, et al. The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation. Am J Transplant 2008;8(10):2086-96
163. Latek R, Fleener C, Lamian V, et al. Assessment of belatacept-mediated costimulation blockade through evaluation of CD80/86-receptor saturation. Transplantation 2009;87(6):926-33
164. Markees TG, Phillips NE, Gordon EJ, et al. 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 1998;101(11):2446-55