共刺激分子與移植免疫耐受_《中國普外基礎與臨床雜志》

作者：

彭勇 ¹ , 龔建平 ²

1.川北醫學院附屬醫院普外科（四川南充 637000）;;
2.重慶醫科大學附屬第二醫院肝膽外科（重慶 400010）;

關鍵詞：

共刺激分子免疫耐受器官移植

視頻：

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摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

目的介紹共刺激分子與器官移植免疫耐受的研究進展。方法復習近年來國內、外相關文獻并作綜述。結果目前有多條共刺激通路與移植免疫的關系已闡明，主要有B7-CD28/CTLA4、CD40-CD154、4-1BB/4-1BBL、ICOS-B7h等。大量研究表明，單一阻斷某個共刺激通路難以達到持久、穩定的免疫耐受，只有協同阻斷或是與其他免疫抑制方法聯合應用時才表現出更好的效果。結論隨著免疫學和分子生物學的發展，T淋巴細胞活化的共刺激通路將被進一步闡明，相信將來還會有新的共刺激分子被發現，為誘導器官移植免疫耐受提供理論依據。

引用本文： 彭勇,龔建平. 共刺激分子與移植免疫耐受. 中國普外基礎與臨床雜志, 2010, 17(6): 552-556. doi: 復制

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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.
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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.

《中國普外基礎與臨床雜志》

共刺激分子與移植免疫耐受

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

《中國普外基礎與臨床雜志》

共刺激分子與移植免疫耐受

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料