The Costimulatory Pathway B7CD28/CTLA4 and the Islets of Langerhans Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

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Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041;

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CD28 CTLA4-Ig Costimulatory pathway Islets of Langerhans transplantation

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ObjectiveTo investigate the significant effect of costimulatory pathway B7CD28/CTLA4 on the islets of Langerhans transplantation. MethodsThe literatures were reviewed to summarize the molecular structure and functions of the pathway and the related animal experiments.ResultsThe costimulatory pathway B7CD28/CTLA4 was one of the signaling pathways of T cells activation and proliferation. If the costimulatory signals were absent, Tlymphocyte would be induced to the clonalanegy. Through blocking the costimulatory pathway mediated by CD28, CTLA4Ig prolonged to the islets of Langerhans survival in recipients. ConclusionBy the studies of the costimulatory pathway, it is helpful to understand the immune mechanism of the survival of islet grafts.

Citation： ZHAO Gaoping,ZHOU Zongguang.. The Costimulatory Pathway B7CD28/CTLA4 and the Islets of Langerhans Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2002, 9(6): 442-444. doi: Copy

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. 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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Costimulatory Pathway B7CD28/CTLA4 and the Islets of Langerhans Transplantation

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