• 四川大學華西醫(yī)院普外科（成都610041);

目的探討B(tài)7CD28/細胞毒T淋巴細胞相關蛋白4（CTLA4）共刺激通路在胰島移植中的重要作用。方法采用文獻回顧的方法對該共刺激通路的分子結構、功能以及有關動物實驗的資料進行綜述。結果B7CD28/CTLA4共刺激通路是T淋巴細胞活化、增殖的信號傳導通路之一，若缺乏共刺激信號，則會導致T淋巴細胞呈克隆無反應狀態(tài)。CTLA4Ig通過阻斷CD28介導的共刺激通路，使胰島移植物在受者體內長期存活。結論通過對B7CD28/CTLA4共刺激通路的研究，有助于了解移植胰島存活的免疫機理。

引用本文： 趙高平,綜述周總光,審校. B7-CD28/CTLA4共刺激通路與胰島移植△. 中國普外基礎與臨床雜志, 2002, 9(6): 442-444. doi: 復制

1. Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Longterm survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig [J]. Science, 1992； 257(5071)∶789.
2. Pearson TC, Alexander DZ, Winn KJ, et al. Transplantation tolerance induced by CTLA4Ig [J]. Transplantation, 1994； 57(12)∶1701.
3. Selvakumar A, White PC, Dupont B. Genomic organization of the mouse Blymphocyte activation antigen B7 [J]. Immunogenetics,1993； 38(4)∶292.
4. Bugeon L, Dallman MJ. Costimulation of T cells [J]. Am J Respir Crit Care Med, 2000； 162(4 Pt 2)∶S164.
5. Lin H, Rathmell JC, Gray GS, et al. Cytotoxic T lymphocyte antigen 4 (CTLA4) blockade accelerates the acute rejection of cardiac allografts in CD28deficient mice: CTLA4 can function independently of CD28 [J]. J Exp Med, 1998； 188(1)∶199.
6. Lumsden JM, Roberts JM, Harris NL, et al. Differential requirement for CD80 and CD80/CD86dependent costimulation in the lung immune response to an influenza virus infection [J]. J Immunol, 2000； 164(1)∶79.
7. Alegre ML, Noel PJ, Eisfelder BJ, et al. Regulation of surface and intracellular expression of CTLA4 on mouse T cells [J]. J Immunol, 1996； 157(11)∶4762.
8. Donner H, Seidl C, Braun J, et al. CTLA4 gene haplotypes cannot protect from IDDM in the presence of highrisk HLA DQ8 or DQ2 alleles in German families [J]. Diabetes, 1998； 47(7)∶1158.
9. Liu Y, Janeway CA Jr. Interferon γ plays a critical role in induced cell death of effector T cell: a possible third mechanism of selftolerance [J]. J Exp Med, 1990； 172(6)∶1735.
10. 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]. J Immunol, 1999； 162(8)∶4983.
11. Gribben JG, Freeman GJ, Boussiotis VA, et al. CTLA4 mediates antigenspecific apoptosis of human T cells [J]. Proc Natl Acad Sci U S A, 1995； 92(3)∶811.
12. Greene JL, Leytze GM, Emswiler J, et al. Covalent dimerization of CD28/CTLA4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions [J]. J Biol Chem, 1996； 271(43)∶26762.
13. Karandikar NJ, Vanderlugt CL, Walunas TL, et al. CTLA4: a negative regulator of autoimmune disease [J]. J Exp Med, 1996； 184(2)∶783.
14. Judge TA, Tang A, Spain LM, et al. The in vivo mechanism of action of CTLA4 Ig [J]. J Immunol, 1996； 156(6)∶2294.
15. Levisetti MG, Padrid PA, Szot GL, et al. Immunosuppressive effects of human CTLA4Ig in a nonhuman primate model of allogeneic pancreatic islet transplantation [J]. J Immunol, 1997； 159(11)∶5187.
16. Steurer W, Nickerson PW, Steele AW, et al.Ex vivo coating of islet cell allografts with murine CTLA4/Fc promotes graft tolerance [J]. J Immunol, 1995； 155(3)∶1165.
17. Chahine AA, Yu M, Mckernan MM, et al. Immunomodulation of pancreatic islet allografts in mice with CTLA4Ig secreting muscle cells [J]. Transplantation, 1995； 59(9)∶1313.
18. O’Rourke RW, Kang SM, Lower JA, et al. A dendritic cell line genetically modified to express CTLA4Ig as a means to prolong islet allograft survival [J]. Transplantation, 2000； 69(7)∶1440.
19. Gainer AL, Korbutt GS, Rajotte RV, et al. Expression of CTLA4Ig by biolistically transfected mouse islets promotes islet allograft survival [J]. Transplantation, 1997； 63(7)∶1017.
20. Deng S, Kaucher T, Liu C, et al. Intraarterial delivery of adenoviral vectors to intact pancreata achieves highly efficient [J]. Diabetes, 1998； 47（SA）∶67.
  1. 1. Lenschow DJ, Zeng Y, Thistlethwaite JR, et al. Longterm survival of xenogeneic pancreatic islet grafts induced by CTLA4Ig [J]. Science, 1992； 257(5071)∶789.
  2. 2. Pearson TC, Alexander DZ, Winn KJ, et al. Transplantation tolerance induced by CTLA4Ig [J]. Transplantation, 1994； 57(12)∶1701.
  3. 3. Selvakumar A, White PC, Dupont B. Genomic organization of the mouse Blymphocyte activation antigen B7 [J]. Immunogenetics,1993； 38(4)∶292.
  4. 4. Bugeon L, Dallman MJ. Costimulation of T cells [J]. Am J Respir Crit Care Med, 2000； 162(4 Pt 2)∶S164.
  5. 5. Lin H, Rathmell JC, Gray GS, et al. Cytotoxic T lymphocyte antigen 4 (CTLA4) blockade accelerates the acute rejection of cardiac allografts in CD28deficient mice: CTLA4 can function independently of CD28 [J]. J Exp Med, 1998； 188(1)∶199.
  6. 6. Lumsden JM, Roberts JM, Harris NL, et al. Differential requirement for CD80 and CD80/CD86dependent costimulation in the lung immune response to an influenza virus infection [J]. J Immunol, 2000； 164(1)∶79.
  7. 7. Alegre ML, Noel PJ, Eisfelder BJ, et al. Regulation of surface and intracellular expression of CTLA4 on mouse T cells [J]. J Immunol, 1996； 157(11)∶4762.
  8. 8. Donner H, Seidl C, Braun J, et al. CTLA4 gene haplotypes cannot protect from IDDM in the presence of highrisk HLA DQ8 or DQ2 alleles in German families [J]. Diabetes, 1998； 47(7)∶1158.
  9. 9. Liu Y, Janeway CA Jr. Interferon γ plays a critical role in induced cell death of effector T cell: a possible third mechanism of selftolerance [J]. J Exp Med, 1990； 172(6)∶1735.
  10. 10. 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]. J Immunol, 1999； 162(8)∶4983.
  11. 11. Gribben JG, Freeman GJ, Boussiotis VA, et al. CTLA4 mediates antigenspecific apoptosis of human T cells [J]. Proc Natl Acad Sci U S A, 1995； 92(3)∶811.
  12. 12. Greene JL, Leytze GM, Emswiler J, et al. Covalent dimerization of CD28/CTLA4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions [J]. J Biol Chem, 1996； 271(43)∶26762.
  13. 13. Karandikar NJ, Vanderlugt CL, Walunas TL, et al. CTLA4: a negative regulator of autoimmune disease [J]. J Exp Med, 1996； 184(2)∶783.
  14. 14. Judge TA, Tang A, Spain LM, et al. The in vivo mechanism of action of CTLA4 Ig [J]. J Immunol, 1996； 156(6)∶2294.
  15. 15. Levisetti MG, Padrid PA, Szot GL, et al. Immunosuppressive effects of human CTLA4Ig in a nonhuman primate model of allogeneic pancreatic islet transplantation [J]. J Immunol, 1997； 159(11)∶5187.
  16. 16. Steurer W, Nickerson PW, Steele AW, et al.Ex vivo coating of islet cell allografts with murine CTLA4/Fc promotes graft tolerance [J]. J Immunol, 1995； 155(3)∶1165.
  17. 17. Chahine AA, Yu M, Mckernan MM, et al. Immunomodulation of pancreatic islet allografts in mice with CTLA4Ig secreting muscle cells [J]. Transplantation, 1995； 59(9)∶1313.
  18. 18. O’Rourke RW, Kang SM, Lower JA, et al. A dendritic cell line genetically modified to express CTLA4Ig as a means to prolong islet allograft survival [J]. Transplantation, 2000； 69(7)∶1440.
  19. 19. Gainer AL, Korbutt GS, Rajotte RV, et al. Expression of CTLA4Ig by biolistically transfected mouse islets promotes islet allograft survival [J]. Transplantation, 1997； 63(7)∶1017.
  20. 20. Deng S, Kaucher T, Liu C, et al. Intraarterial delivery of adenoviral vectors to intact pancreata achieves highly efficient [J]. Diabetes, 1998； 47（SA）∶67.