Costimulatory Molecules and Immune Tolerance_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

PENG Yong ¹ , GONG Jianping ²

1.Department of General Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China;;
2.Department of Hepotabiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China;

Corresponding author：

Keywords：

Costimulatory molecules; Immune tolerance; Organ transplantation

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Objective To summarize the role of costimulatory molecules in inducing immune tolerance of organ transplantation. Methods Domestic and international publications online involving costimulatory molecules and immune tolerance in recent years were collected and reviewed. Results The relationship between costimulatory pathways and transplantation immunity has already been clarified in recent years. The main costimulatory molecules alreadly found mainly include B7-CD28/CTLA4, CD40-CD154, 4-1BB/4-1BBL, and ICOS-B7h, etc. Costimulatory pathways com-inhibition or combining with other immunosuppression methods could obtain stable and long lasting immune tolerance. Conclusions With the development of immunology and molecular biology, costimulatory pathways of T lymphocyte activation will be further interpreted. Other new costimulatory molecules will be discovered in the future, which will afford theory evidence for inducing immune tolerance.

Citation： PENG Yong,GONG Jianping. Costimulatory Molecules and Immune Tolerance. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(6): 552-556. doi: Copy

1.	Brown RS, Belton AM, Martin JM, et al. Evolution of quality at the Organ Center of the Organ Procurement and Transplantation Network/United Network for Organ Sharing [J]. Prog Transplant, 2009; 19(3): 221-226.
2.	Daniel V, Opelz G. Clinical relevance of immune monitoring in solid organ transplantation [J]. Int Rev Immunol, 2009； 28(3-4): 155-184.
3.	Rath T, Oliveira-Frick V. Mutagenicity of immunosuppressive medications among renal transplant recipients [J]. Am J Nephrol, 2009； 30(6): 514-520.
4.	Xie B, Chen J, Xia J, et al. Combined costimulation blockade inhibits accelerated rejection mediated by alloantigen-primed memory T cells in mice [J]. Immunol Invest, 2009； 38(7): 639-651.
5.	Ritter T, Nosov M, Griffin MD. Gene therapy in transplantation: Toward clinical trials [J]. Curr Opin Mol Ther, 2009； 11(5): 504-512.
6.	Li S, Kuang A, Huang R. Can proliferation signal inhibitor-induced Tregs really reflect transplantation tolerance in clinical solid organ transplantation? [J]. Int Rev Immunol, 2009； 28(5): 367-375.
7.	de Jager SC, Canté-Barrett K, Bot I, et al. Impaired effector memory T-cell regulation facilitates graft versus host disease in CCR7-deficient bone marrow transplant chimeras [J]. Transplantation, 2009； 88(5): 631-639.
8.	Du JF, Li SY, Yu B. Rapamycin-rather than FK506-might promote allograft tolerance induced by CD4+CD25+ regulatory T cells [J]. Surgery, 2009； 142(1): 67-73.
9.	Martins PN. Impact of donor and recipient age on allograft tolerance [J]. Exp Clin Transplant, 2009； 7（2）: 67-77.
10.	Kim SY, Kim DW, Choi JY, et al. Full donor chimerism using stem-cell transplantation for tolerance induction in the human leukocyte antigen-matched liver transplant setting [J]. Transplantation, 2009； 88(4): 601-603.
11.	Zheng J, Liu Y, Qin G, et al. Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells [J]. J Immunol, 2009； 183(6): 3742-3750.
12.	Graves SS, Stone D, Loretz C, et al. Establishment of long-term tolerance to SRBC in dogs by recombinant canine CTLA4-Ig [J]. Transplantation, 2009； 88(3): 317-322.
13.	Schroeder RA, Marroquin CE, Kuo PC. Tolerance and the “Holy Grail” of transplantation [J]. J Surg Res, 2003; 111(1): 109-119.
14.	Rivas MN, Weatherly K, Hazzan M, et al. Reviving function in CD4+ T cells adapted to persistent systemic antigen [J]. J Immunol, 2009； 183(7): 4284-4291.
15.	Shilling RA, Clay BS, Tesciuba AG, et al. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo [J]. Cell Immunol, 2009； 259(2): 177-184.
16.	Riley JL, June CH. The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation [J]. Blood, 2005； 105(1): 13-21.
17.	Halloran PF. T-cell activation pathways: a transplantation perspective [J]. Transplant Proc, 1999； 31(1-2): 769-771.
18.	Brunet JF, Denizot F, Luciani MF, et al. A new member of the immunoglobulin superfamily-CTLA4 [J]. Nature, 1987； 328(6127): 267-270.
19.	Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 costimulation: a review [J]. Crit Rev Immunol, 1998； 18(5): 389-418.
20.	Tector M, Khatri BO, Kozinski K, et al. Biochemical analysis of CTLA-4 immunoreactive material from human blood [J]. BMC Immunol, 2009； 10: 51.
21.	Kroczek R, Hamelmann E. T-cell costimulatory molecules: optimal targets for the treatment of allergic airway disease with monoclonal antibodies [J]. J Allergy Clin Immunol, 2005； 116(4): 906-909.
22.	Peggs KS, Quezada SA, Chambers CA, et al. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies [J]. J Exp Med, 2009； 206(8): 1717-1725.
23.	Jochum C, Beste M, Stone D, et al. Development and in vitro characterization of canine CD40-Ig [J]. Vet Immunol Immunopathol, 2008； 123(3-4): 260-265.
24.	Wang GM, Ma JB, Jin YZ, et al. Long-term survival of cardiac allografts induced by cyclophosphamide combined with CTLA4Ig-gene transfer mediated by adenoviral vector [J]. Transplant Proc, 2006； 38(9): 3043-3045.
25.	Lu S, Yu Y, Gao Y, et al. Immunological inhibition of transplanted liver allografts by adeno-associated virus vector encoding CTLA4Ig in rats[J]. Hepatobiliary Pancreat Dis Int, 2008； 7(3): 258-263.
26.	Xu H, Yan J, Huang Y, et al. Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization[J]. Blood, 2008； 111(6): 3266-3275.
27.	Shoker A, George D, Yang H, et al. Heightened CD40 ligand gene expression in peripheral CD4+ T cells from patients with kidney allograft rejection [J]. Transplantation, 2000; 70(3): 497-505.
28.	Kover KL, Geng Z, Hess DM, et al. Anti-CD154 (CD40L) prevents recurrence of diabetes in islet isografts in the DR-BB rat [J]. Diabetes, 2000； 49(10): 1666-1670.
29.	Graca L, Honey K, Adams E, et al. Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance [J]. J Immunol， 2000； 165(9): 4783-4786.
30.	Shimizu K, Schnbeck U, Mach F, et al. Host CD40 ligand deficiency induces long-term allograft survival and donor-specific tolerance in mouse cardiac transplantation but does not prevent graft arteriosclerosis [J]. J Immunol, 2000； 165(6): 3506-3518.
31.	Bauquet AT, Jin H, Paterson AM, et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells [J]. Nat Immunol, 2009； 10(2): 167-175.
32.	Chen Y, Liu H, Liu Z, et al. Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation [J]. Am J Surg, 2009； 198(2): 244-249.
33.	Pan XC, Guo L, Deng YB, et al. Further study of anti-ICOS immunotherapy for rat cardiac allograft rejection [J]. Surg Today, 2008; 38(9): 815-825.
34.	Kwon BS, Kestler DP, Eshhar Z, et al. Expression characteristics of two potential T cell mediator genes [J]. Cell Immunol, 1989； 121(2): 414-422.
35.	Goodwin RG, Din WS, Davis-Smith T, et al. Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor[J]. Eur J Immunol, 1993； 23(10): 2631-2641.
36.	Xu K, Li C, Pan X, et al. Study of relieving graft-versus-host disease by blocking CD137-CD137 ligand costimulatory pathway in vitro [J]. Int J Hematol, 2007； 86(1): 84-90.
37.	Huang BJ, Yin H, Huang YF, et al. Gene therapy using adenoviral vector encoding 4-1BBIg gene significantly prolonged murine cardiac allograft survival [J]. Transpl Immunol, 2006； 16(2): 88-94.

1. Brown RS, Belton AM, Martin JM, et al. Evolution of quality at the Organ Center of the Organ Procurement and Transplantation Network/United Network for Organ Sharing [J]. Prog Transplant, 2009; 19(3): 221-226.
2. Daniel V, Opelz G. Clinical relevance of immune monitoring in solid organ transplantation [J]. Int Rev Immunol, 2009； 28(3-4): 155-184.
3. Rath T, Oliveira-Frick V. Mutagenicity of immunosuppressive medications among renal transplant recipients [J]. Am J Nephrol, 2009； 30(6): 514-520.
4. Xie B, Chen J, Xia J, et al. Combined costimulation blockade inhibits accelerated rejection mediated by alloantigen-primed memory T cells in mice [J]. Immunol Invest, 2009； 38(7): 639-651.
5. Ritter T, Nosov M, Griffin MD. Gene therapy in transplantation: Toward clinical trials [J]. Curr Opin Mol Ther, 2009； 11(5): 504-512.
6. Li S, Kuang A, Huang R. Can proliferation signal inhibitor-induced Tregs really reflect transplantation tolerance in clinical solid organ transplantation? [J]. Int Rev Immunol, 2009； 28(5): 367-375.
7. de Jager SC, Canté-Barrett K, Bot I, et al. Impaired effector memory T-cell regulation facilitates graft versus host disease in CCR7-deficient bone marrow transplant chimeras [J]. Transplantation, 2009； 88(5): 631-639.
8. Du JF, Li SY, Yu B. Rapamycin-rather than FK506-might promote allograft tolerance induced by CD4+CD25+ regulatory T cells [J]. Surgery, 2009； 142(1): 67-73.
9. Martins PN. Impact of donor and recipient age on allograft tolerance [J]. Exp Clin Transplant, 2009； 7（2）: 67-77.
10. Kim SY, Kim DW, Choi JY, et al. Full donor chimerism using stem-cell transplantation for tolerance induction in the human leukocyte antigen-matched liver transplant setting [J]. Transplantation, 2009； 88(4): 601-603.
11. Zheng J, Liu Y, Qin G, et al. Efficient induction and expansion of human alloantigen-specific CD8 regulatory T cells from naive precursors by CD40-activated B cells [J]. J Immunol, 2009； 183(6): 3742-3750.
12. Graves SS, Stone D, Loretz C, et al. Establishment of long-term tolerance to SRBC in dogs by recombinant canine CTLA4-Ig [J]. Transplantation, 2009； 88(3): 317-322.
13. Schroeder RA, Marroquin CE, Kuo PC. Tolerance and the “Holy Grail” of transplantation [J]. J Surg Res, 2003; 111(1): 109-119.
14. Rivas MN, Weatherly K, Hazzan M, et al. Reviving function in CD4+ T cells adapted to persistent systemic antigen [J]. J Immunol, 2009； 183(7): 4284-4291.
15. Shilling RA, Clay BS, Tesciuba AG, et al. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo [J]. Cell Immunol, 2009； 259(2): 177-184.
16. Riley JL, June CH. The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation [J]. Blood, 2005； 105(1): 13-21.
17. Halloran PF. T-cell activation pathways: a transplantation perspective [J]. Transplant Proc, 1999； 31(1-2): 769-771.
18. Brunet JF, Denizot F, Luciani MF, et al. A new member of the immunoglobulin superfamily-CTLA4 [J]. Nature, 1987； 328(6127): 267-270.
19. Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 costimulation: a review [J]. Crit Rev Immunol, 1998； 18(5): 389-418.
20. Tector M, Khatri BO, Kozinski K, et al. Biochemical analysis of CTLA-4 immunoreactive material from human blood [J]. BMC Immunol, 2009； 10: 51.
21. Kroczek R, Hamelmann E. T-cell costimulatory molecules: optimal targets for the treatment of allergic airway disease with monoclonal antibodies [J]. J Allergy Clin Immunol, 2005； 116(4): 906-909.
22. Peggs KS, Quezada SA, Chambers CA, et al. Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies [J]. J Exp Med, 2009； 206(8): 1717-1725.
23. Jochum C, Beste M, Stone D, et al. Development and in vitro characterization of canine CD40-Ig [J]. Vet Immunol Immunopathol, 2008； 123(3-4): 260-265.
24. Wang GM, Ma JB, Jin YZ, et al. Long-term survival of cardiac allografts induced by cyclophosphamide combined with CTLA4Ig-gene transfer mediated by adenoviral vector [J]. Transplant Proc, 2006； 38(9): 3043-3045.
25. Lu S, Yu Y, Gao Y, et al. Immunological inhibition of transplanted liver allografts by adeno-associated virus vector encoding CTLA4Ig in rats[J]. Hepatobiliary Pancreat Dis Int, 2008； 7(3): 258-263.
26. Xu H, Yan J, Huang Y, et al. Costimulatory blockade of CD154-CD40 in combination with T-cell lymphodepletion results in prevention of allogeneic sensitization[J]. Blood, 2008； 111(6): 3266-3275.
27. Shoker A, George D, Yang H, et al. Heightened CD40 ligand gene expression in peripheral CD4+ T cells from patients with kidney allograft rejection [J]. Transplantation, 2000; 70(3): 497-505.
28. Kover KL, Geng Z, Hess DM, et al. Anti-CD154 (CD40L) prevents recurrence of diabetes in islet isografts in the DR-BB rat [J]. Diabetes, 2000； 49(10): 1666-1670.
29. Graca L, Honey K, Adams E, et al. Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance [J]. J Immunol， 2000； 165(9): 4783-4786.
30. Shimizu K, Schnbeck U, Mach F, et al. Host CD40 ligand deficiency induces long-term allograft survival and donor-specific tolerance in mouse cardiac transplantation but does not prevent graft arteriosclerosis [J]. J Immunol, 2000； 165(6): 3506-3518.
31. Bauquet AT, Jin H, Paterson AM, et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells [J]. Nat Immunol, 2009； 10(2): 167-175.
32. Chen Y, Liu H, Liu Z, et al. Blockade of inducible costimulator pathway to prevent acute rejection in rat liver transplantation [J]. Am J Surg, 2009； 198(2): 244-249.
33. Pan XC, Guo L, Deng YB, et al. Further study of anti-ICOS immunotherapy for rat cardiac allograft rejection [J]. Surg Today, 2008; 38(9): 815-825.
34. Kwon BS, Kestler DP, Eshhar Z, et al. Expression characteristics of two potential T cell mediator genes [J]. Cell Immunol, 1989； 121(2): 414-422.
35. Goodwin RG, Din WS, Davis-Smith T, et al. Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor[J]. Eur J Immunol, 1993； 23(10): 2631-2641.
36. Xu K, Li C, Pan X, et al. Study of relieving graft-versus-host disease by blocking CD137-CD137 ligand costimulatory pathway in vitro [J]. Int J Hematol, 2007； 86(1): 84-90.
37. Huang BJ, Yin H, Huang YF, et al. Gene therapy using adenoviral vector encoding 4-1BBIg gene significantly prolonged murine cardiac allograft survival [J]. Transpl Immunol, 2006； 16(2): 88-94.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Costimulatory Molecules and Immune Tolerance

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