• 1.昆明醫(yī)學院第二附屬醫(yī)院肝膽胰一病區(qū)（昆明 650101）;;
  • 2.昆明市第一人民醫(yī)院暨昆明醫(yī)學院附屬甘美醫(yī)院肝移植中心（昆明 650011）;

目的  總結(jié)胰腺移植免疫耐受的研究進展。方法  分析近年來有關(guān)胰腺移植免疫耐受研究進展的文獻報道。 結(jié)果  外周性耐受及中樞性耐受是誘導免疫耐受的主要方法，其中通過供體特異性骨髓細胞輸注誘導嵌合體形成是目前的研究熱點。結(jié)論  供體特異性骨髓細胞輸注聯(lián)合一種或多種外周性耐受方法有望誘導胰腺移植免疫耐受，但需進行深入研究。

引用本文： 魏曉平,李立. 胰腺移植免疫耐受研究進展. 中國普外基礎(chǔ)與臨床雜志, 2008, 15(12): 883-886. doi: 復制

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 濤， 羅 軍， 溫 浩. 細胞凋亡在大鼠胰腺移植急性排斥反應中的作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 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. 鄭樹森， 于吉人， 王偉林主編. 胰腺移植 [M]. 第1版. 北京： 人民衛(wèi)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. 李紀鵬， 黃 怡， 王為忠， 等. TGF-β1基因修飾的未成熟樹突狀細胞對小腸移植大鼠外周血及移植腸浸潤T細胞的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 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, 黃萃庭. 供體脾細胞在大鼠胰十二指腸移植中抗免疫排斥作用的初步觀察 [J]. 中華實驗外科雜志, 1989; 6(3)∶106.
24. 周 峰, 萬赤丹, 熊炯炘, 等. 供體特異性輸血對大鼠胰十二指腸移植的保護作用 [J]. 中華實驗外科雜志, 2004; 21(12)∶1477.
25. 韓曙光, 徐澤寬, 張 軒, 等. 可誘導性共刺激分子單抗聯(lián)合細胞毒T淋巴細胞4Ig在大鼠胰腺移植中的作用 [J]. 中華實驗外科雜志, 2007; 24(4)∶ 420.
26. 孟令祥, 胡偉明, 張肇達, 等. Ad-CTLA-4Ig基因?qū)雽σ仁改c移植大鼠免疫耐受的實驗研究 [J]. 四川大學學報(醫(yī)學版), 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. 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. 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. 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. 4. 李 濤， 羅 軍， 溫 浩. 細胞凋亡在大鼠胰腺移植急性排斥反應中的作用 [J]. 中國普外基礎(chǔ)與臨床雜志, 2007; 14（1）∶59.
  5. 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. 6. Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity [J]. Nat Rev Immunol, 2007; 7(8)∶622.
  7. 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. 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. 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. 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. 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. 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. 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. 14. 鄭樹森， 于吉人， 王偉林主編. 胰腺移植 [M]. 第1版. 北京： 人民衛(wèi)生出版社， 2002∶59~61.
  15. 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. 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. 17. 李紀鵬， 黃 怡， 王為忠， 等. TGF-β1基因修飾的未成熟樹突狀細胞對小腸移植大鼠外周血及移植腸浸潤T細胞的影響 [J]. 中國普外基礎(chǔ)與臨床雜志, 2008; 15(2)∶96.
  18. 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. 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. 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. 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. 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. 23. 冷希圣, 黃萃庭. 供體脾細胞在大鼠胰十二指腸移植中抗免疫排斥作用的初步觀察 [J]. 中華實驗外科雜志, 1989; 6(3)∶106.
  24. 24. 周 峰, 萬赤丹, 熊炯炘, 等. 供體特異性輸血對大鼠胰十二指腸移植的保護作用 [J]. 中華實驗外科雜志, 2004; 21(12)∶1477.
  25. 25. 韓曙光, 徐澤寬, 張 軒, 等. 可誘導性共刺激分子單抗聯(lián)合細胞毒T淋巴細胞4Ig在大鼠胰腺移植中的作用 [J]. 中華實驗外科雜志, 2007; 24(4)∶ 420.
  26. 26. 孟令祥, 胡偉明, 張肇達, 等. Ad-CTLA-4Ig基因?qū)雽σ仁改c移植大鼠免疫耐受的實驗研究 [J]. 四川大學學報(醫(yī)學版), 2007; 38(3)∶ 374.
  27. 27. Bitter-Suermann H. Survival of unmodified spleen allografts in rats [J]. Nature, 1974; 247(441)∶465.
  28. 28. Schulak JA, Engelstad KM. Immunologic consequences of combined pancreas-spleen transplantation in the rat [J]. J Surg Res, 1989; 47(1)∶52.
  29. 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. 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. 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. 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. 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. 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. 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. 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. 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.