Current Research Advancement of Immune Tolerance in Pancreas Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WEI Xiaoping ¹ , LI Li ²

1.Department of Hepatobiliary Pancreatic Surgery One， The Second Affiliated Hospital of Kunming Medical College， Kunming 650101， China;;
2.Liver Transplantation Centre, The First People’s Hospital of Kunming City and Affiliated Ganmei Hospital of Kunming Medical College, Kunming 650011, China;

Corresponding author：

Keywords：

Pancreas transplantation; Immune tolerance; Transplantation chimerism

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Objective To summarize the advancement of immune tolerance in pancreas transplantation.Methods Relevant literatures about immune tolerance in pancreas transplantation, which were published recently domestic and abroad were collected and reviewed. Results The main methods to induce immune tolerance are peripheral tolerance and central tolerance. The induction of chimerism by infusion of donor-specific bone marrow cells is the research hot spot recently. Conclusion The infusion of donor-specific bone marrow cells in combination with one or more peripheral tolerance maybe can induce immune tolerance successfully. However, it should be researched further.

Citation： WEI Xiaoping,LI Li. Current Research Advancement of Immune Tolerance in Pancreas Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(12): 883-886. doi: Copy

1.	Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004 [J]. Clin Transplant, 2005; 19(4)∶433.
2.	Masaki H, Appel MC, Leahy L, et al. Anti-mouse CD154 antibody treatment facilitates generation of mixed xenogeneic rat hematopoietic chimerism, prevents wasting disease and prolongs xenograft survival in mice [J]. Xenotransplantation, 2006; 13(3)∶224.
3.	Pan H, Lu HM, Hu WM, et al. Anti-CD25 mAb, anti-IL2 mAb, and IL2 block tolerance induction through anti-CD154 mAb and rapamycin in xenogeneic islet transplantation [J]. Transplant Proc, 2007; 39(10)∶3452.
4.	李涛，罗军，温浩. 细胞凋亡在大鼠胰腺移植急性排斥反应中的作用 [J]. 中国普外基础与临床杂志, 2007; 14（1）∶59.
5.	Wang Z, Davies JD. CD8 blockade promotes antigen responsiveness to nontolerizing antigen in tolerant mice by inhibiting apoptosis of CD4+ T cells [J]. J Immunol, 2007; 178(10)∶6148.
6.	Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity [J]. Nat Rev Immunol, 2007; 7(8)∶622.
7.	Wu X, Guo R, Wang Y, et al. The role of ICAM-1 in endotoxin-induced acute renal failure [J]. Am J Physiol Renal Physiol, 2007; 293(4)∶F1262.
8.	Filby A, Seddon B, Kleczkowska J, et al. Fyn regulates the duration of TCR engagement needed for commitment to effector function [J]. J Immunol, 2007; 179(7)∶4635.
9.	Foell J, Hewes B, Mittler RS. T cell costimulatory and inhibitory receptors as therapeutic targets for inducing anti-tumor immunity [J]. Curr Cancer Drug Targets, 2007; 7(1)∶55.
10.	Scharpf J, Strome M, Siemionow M. Immunomodulation with anti-alphabeta T-cell receptor monoclonal antibodies in combination with cyclosporine A improves regeneration in nerve allografts [J]. Microsurgery, 2006; 26(8)∶599.
11.	Lee JH, Ha J, Kim SH, et al. IL-2 pathway blocking in combination with anti-CD154 synergistically establishes mixed macrochimerism with limited dose of bone marrow cells and prolongs skin graft survival in mice [J]. J Korean Med Sci, 2006; 21(6)∶1005.
12.	Chavez H, Beaudreuil S, Abbed K, et al. Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade [J]. Transpl Immunol, 2007; 17(4)∶243.
13.	Li ZL, Xue WJ, Tian PX, et al. Prolongation of islet allograft survival by coexpression of CTLA4Ig and CD40LIg in mice [J]. Transplant Proc, 2007; 39(10)∶3436.
14.	郑树森，于吉人，王伟林主编. 胰腺移植 [M]. 第1版. 北京：人民卫生出版社， 2002∶59~61.
15.	Yamazaki M, Pearson T, Brehm MA, et al. Different mechanisms control peripheral and central tolerance in hematopoietic chimeric mice [J]. Am J Transplant, 2007; 7(7)∶1710.
16.	Starzl TE, Demetris AJ, Trucco M, et al. Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation [J]. Transplantation, 1993; 55(6)∶1272.
17.	李纪鹏，黄怡，王为忠，等. TGF-β1基因修饰的未成熟树突状细胞对小肠移植大鼠外周血及移植肠浸润T细胞的影响 [J]. 中国普外基础与临床杂志, 2008; 15(2)∶96.
18.	Ito H, Takeuchi Y, Shaffer J, et al. Anti-CD40L monoclonal antibodies can replace anti-CD4 monoclonal antibodies for the nonmyeloablative induction of mixed xenogeneic chimerism [J]. Transplantation, 2006; 82(2)∶251.
19.	Takeuchi Y, Ito H, Kurtz J, et al. Earlier low-dose TBI or DST overcomes CD8+ T-cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L [J]. Am J Transplant, 2004; 4(1)∶31.
20.	Kurtz J, Shaffer J, Lie A, et al. Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells [J]. Blood, 2004; 103(11)∶4336.
21.	Ito T, Stepkowski SM, Kahan BD. Soluble antigen and cyclosporine-induced specific unresponsiveness in rats. Frequency of alloantigen-specific T cytotoxic cells in normal, sensitized, and unresponsive rats [J]. Transplantation, 1990; 49(2)∶422.
22.	Ito T, Uchikoshi F, Tori M, et al. Immunological characteristics of pancreas transplantation: review and our experimental experience [J]. Pancreas, 2003; 27(1)∶31.
23.	冷希圣, 黄萃庭. 供体脾细胞在大鼠胰十二指肠移植中抗免疫排斥作用的初步观察 [J]. 中华实验外科杂志, 1989; 6(3)∶106.
24.	周峰, 万赤丹, 熊炯炘, 等. 供体特异性输血对大鼠胰十二指肠移植的保护作用 [J]. 中华实验外科杂志, 2004; 21(12)∶1477.
25.	韩曙光, 徐泽宽, 张轩, 等. 可诱导性共刺激分子单抗联合细胞毒T淋巴细胞4Ig在大鼠胰腺移植中的作用 [J]. 中华实验外科杂志, 2007; 24(4)∶ 420.
26.	孟令祥, 胡伟明, 张肇达, 等. Ad-CTLA-4Ig基因导入对胰十二指肠移植大鼠免疫耐受的实验研究 [J]. 四川大学学报(医学版), 2007; 38(3)∶ 374.
27.	Bitter-Suermann H. Survival of unmodified spleen allografts in rats [J]. Nature, 1974; 247(441)∶465.
28.	Schulak JA, Engelstad KM. Immunologic consequences of combined pancreas-spleen transplantation in the rat [J]. J Surg Res, 1989; 47(1)∶52.
29.	Sakuma Y, Sato Y, Inoue S, et al. Lympho-myeloid chimerism achieved by spleen graft of green fluorescent protein transgenic rat in a combined pancreas transplantation model (TI03-029) [J]. Transpl Immunol, 2004; 12(2)∶115.
30.	Zhong T, Liu Y, Jiang J, et al. Long-term limb allograft survival using a short course of anti-CD45RB monoclonal antibody, LF 15-0195, and rapamycin in a mouse model [J]. Transplantation, 2007; 84(12)∶1636.
31.	Masaki Y, Suzuki K, Yan H, et al. Quantitative aspects of microchimerism after rat small bowel and pancreaticoduodenal transplantation [J]. Transplant Proc, 2000; 32(7)∶2483.
32.	Hayashi H, Toki J, Zhexiong L, et al. Long-term (>1 year) analyses of chimerism and tolerance in mixed allogeneic chimeric mice using normal mouse combinations [J]. Stem Cells, 2000; 18(4)∶273.
33.	Jin T, Toki J, Inaba M, Sugiura K, et al. A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein [J]. Transplantation, 2001; 71(12)∶1725.
34.	Drevillon C, Elian N, Zinzindohoue F, et al. Prolonged improvement of total pancreatic allograft function by previous intrathymic bone marrow cell injection in rats [J]. Eur Surg Res, 2003; 35(1)∶1.
35.	Burke GW, Ciancio G, Garcia-Morales R, et al. Evidence for microchimerism in peripheral blood, bone marrow, and skin following donor bone marrow/kidney-pancreas transplantation at 3 years [J]. Transplant Proc, 1998; 30(4)∶1555.
36.	Corry RJ, Chakrabarti PK, Shapiro R, et al. Simultaneous administration of adjuvant donor bone marrow in pancreas transplant recipients [J]. Ann Surg, 1999; 230(3)∶372.
37.	Kuhr CS, Nelson K, Gaur L, et al. Induced microchimerism by spleen reperfusion affords no immunological advantage in pancreas transplantation [J]. Transplant Proc, 2003; 35(2)∶878.

1. Gruessner AC, Sutherland DE. Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004 [J]. Clin Transplant, 2005; 19(4)∶433.
2. Masaki H, Appel MC, Leahy L, et al. Anti-mouse CD154 antibody treatment facilitates generation of mixed xenogeneic rat hematopoietic chimerism, prevents wasting disease and prolongs xenograft survival in mice [J]. Xenotransplantation, 2006; 13(3)∶224.
3. Pan H, Lu HM, Hu WM, et al. Anti-CD25 mAb, anti-IL2 mAb, and IL2 block tolerance induction through anti-CD154 mAb and rapamycin in xenogeneic islet transplantation [J]. Transplant Proc, 2007; 39(10)∶3452.
4. 李涛，罗军，温浩. 细胞凋亡在大鼠胰腺移植急性排斥反应中的作用 [J]. 中国普外基础与临床杂志, 2007; 14（1）∶59.
5. Wang Z, Davies JD. CD8 blockade promotes antigen responsiveness to nontolerizing antigen in tolerant mice by inhibiting apoptosis of CD4+ T cells [J]. J Immunol, 2007; 178(10)∶6148.
6. Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity [J]. Nat Rev Immunol, 2007; 7(8)∶622.
7. Wu X, Guo R, Wang Y, et al. The role of ICAM-1 in endotoxin-induced acute renal failure [J]. Am J Physiol Renal Physiol, 2007; 293(4)∶F1262.
8. Filby A, Seddon B, Kleczkowska J, et al. Fyn regulates the duration of TCR engagement needed for commitment to effector function [J]. J Immunol, 2007; 179(7)∶4635.
9. Foell J, Hewes B, Mittler RS. T cell costimulatory and inhibitory receptors as therapeutic targets for inducing anti-tumor immunity [J]. Curr Cancer Drug Targets, 2007; 7(1)∶55.
10. Scharpf J, Strome M, Siemionow M. Immunomodulation with anti-alphabeta T-cell receptor monoclonal antibodies in combination with cyclosporine A improves regeneration in nerve allografts [J]. Microsurgery, 2006; 26(8)∶599.
11. Lee JH, Ha J, Kim SH, et al. IL-2 pathway blocking in combination with anti-CD154 synergistically establishes mixed macrochimerism with limited dose of bone marrow cells and prolongs skin graft survival in mice [J]. J Korean Med Sci, 2006; 21(6)∶1005.
12. Chavez H, Beaudreuil S, Abbed K, et al. Absence of CD4CD25 regulatory T cell expansion in renal transplanted patients treated in vivo with Belatacept mediated CD28-CD80/86 blockade [J]. Transpl Immunol, 2007; 17(4)∶243.
13. Li ZL, Xue WJ, Tian PX, et al. Prolongation of islet allograft survival by coexpression of CTLA4Ig and CD40LIg in mice [J]. Transplant Proc, 2007; 39(10)∶3436.
14. 郑树森，于吉人，王伟林主编. 胰腺移植 [M]. 第1版. 北京：人民卫生出版社， 2002∶59~61.
15. Yamazaki M, Pearson T, Brehm MA, et al. Different mechanisms control peripheral and central tolerance in hematopoietic chimeric mice [J]. Am J Transplant, 2007; 7(7)∶1710.
16. Starzl TE, Demetris AJ, Trucco M, et al. Chimerism and donor-specific nonreactivity 27 to 29 years after kidney allotransplantation [J]. Transplantation, 1993; 55(6)∶1272.
17. 李纪鹏，黄怡，王为忠，等. TGF-β1基因修饰的未成熟树突状细胞对小肠移植大鼠外周血及移植肠浸润T细胞的影响 [J]. 中国普外基础与临床杂志, 2008; 15(2)∶96.
18. Ito H, Takeuchi Y, Shaffer J, et al. Anti-CD40L monoclonal antibodies can replace anti-CD4 monoclonal antibodies for the nonmyeloablative induction of mixed xenogeneic chimerism [J]. Transplantation, 2006; 82(2)∶251.
19. Takeuchi Y, Ito H, Kurtz J, et al. Earlier low-dose TBI or DST overcomes CD8+ T-cell-mediated alloresistance to allogeneic marrow in recipients of anti-CD40L [J]. Am J Transplant, 2004; 4(1)∶31.
20. Kurtz J, Shaffer J, Lie A, et al. Mechanisms of early peripheral CD4 T-cell tolerance induction by anti-CD154 monoclonal antibody and allogeneic bone marrow transplantation: evidence for anergy and deletion but not regulatory cells [J]. Blood, 2004; 103(11)∶4336.
21. Ito T, Stepkowski SM, Kahan BD. Soluble antigen and cyclosporine-induced specific unresponsiveness in rats. Frequency of alloantigen-specific T cytotoxic cells in normal, sensitized, and unresponsive rats [J]. Transplantation, 1990; 49(2)∶422.
22. Ito T, Uchikoshi F, Tori M, et al. Immunological characteristics of pancreas transplantation: review and our experimental experience [J]. Pancreas, 2003; 27(1)∶31.
23. 冷希圣, 黄萃庭. 供体脾细胞在大鼠胰十二指肠移植中抗免疫排斥作用的初步观察 [J]. 中华实验外科杂志, 1989; 6(3)∶106.
24. 周峰, 万赤丹, 熊炯炘, 等. 供体特异性输血对大鼠胰十二指肠移植的保护作用 [J]. 中华实验外科杂志, 2004; 21(12)∶1477.
25. 韩曙光, 徐泽宽, 张轩, 等. 可诱导性共刺激分子单抗联合细胞毒T淋巴细胞4Ig在大鼠胰腺移植中的作用 [J]. 中华实验外科杂志, 2007; 24(4)∶ 420.
26. 孟令祥, 胡伟明, 张肇达, 等. Ad-CTLA-4Ig基因导入对胰十二指肠移植大鼠免疫耐受的实验研究 [J]. 四川大学学报(医学版), 2007; 38(3)∶ 374.
27. Bitter-Suermann H. Survival of unmodified spleen allografts in rats [J]. Nature, 1974; 247(441)∶465.
28. Schulak JA, Engelstad KM. Immunologic consequences of combined pancreas-spleen transplantation in the rat [J]. J Surg Res, 1989; 47(1)∶52.
29. Sakuma Y, Sato Y, Inoue S, et al. Lympho-myeloid chimerism achieved by spleen graft of green fluorescent protein transgenic rat in a combined pancreas transplantation model (TI03-029) [J]. Transpl Immunol, 2004; 12(2)∶115.
30. Zhong T, Liu Y, Jiang J, et al. Long-term limb allograft survival using a short course of anti-CD45RB monoclonal antibody, LF 15-0195, and rapamycin in a mouse model [J]. Transplantation, 2007; 84(12)∶1636.
31. Masaki Y, Suzuki K, Yan H, et al. Quantitative aspects of microchimerism after rat small bowel and pancreaticoduodenal transplantation [J]. Transplant Proc, 2000; 32(7)∶2483.
32. Hayashi H, Toki J, Zhexiong L, et al. Long-term (>1 year) analyses of chimerism and tolerance in mixed allogeneic chimeric mice using normal mouse combinations [J]. Stem Cells, 2000; 18(4)∶273.
33. Jin T, Toki J, Inaba M, Sugiura K, et al. A novel strategy for organ allografts using sublethal (7 Gy) irradiation followed by injection of donor bone marrow cells via portal vein [J]. Transplantation, 2001; 71(12)∶1725.
34. Drevillon C, Elian N, Zinzindohoue F, et al. Prolonged improvement of total pancreatic allograft function by previous intrathymic bone marrow cell injection in rats [J]. Eur Surg Res, 2003; 35(1)∶1.
35. Burke GW, Ciancio G, Garcia-Morales R, et al. Evidence for microchimerism in peripheral blood, bone marrow, and skin following donor bone marrow/kidney-pancreas transplantation at 3 years [J]. Transplant Proc, 1998; 30(4)∶1555.
36. Corry RJ, Chakrabarti PK, Shapiro R, et al. Simultaneous administration of adjuvant donor bone marrow in pancreas transplant recipients [J]. Ann Surg, 1999; 230(3)∶372.
37. Kuhr CS, Nelson K, Gaur L, et al. Induced microchimerism by spleen reperfusion affords no immunological advantage in pancreas transplantation [J]. Transplant Proc, 2003; 35(2)∶878.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Current Research Advancement of Immune Tolerance in Pancreas Transplantation

Abstract Full text Figures/Tables Video References Cited by

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