抗原特异性CD4^+CD25^+T细胞对同种异体胰岛移植影响及作用机制研究  

Mechanism of donor antigen-specific CD4^+CD25^+ regulatory T cells on prolonging islet grafts survival

作　　者：张梅[1] 徐书杭[1] 徐瑜[1] 刘翠萍[1] 茅晓东[1] 徐宽枫[1] 刘超[1] 

机构地区：[1]南京医科大学第一附属医院内分泌科,江苏南京210029

出　　处：《中国普通外科杂志》2008年第9期878-882,共5页China Journal of General Surgery

基　　金：江苏省政府医学重点学科项目基金资助(苏卫科教2001-34)

摘　　要：目的探讨抗原特异性CD4+CD25+Treg细胞免疫对同种异体胰岛急性移植排斥反应的影响和机制。方法用MACS分选供体抗原特异性CD4+CD25+Treg细胞免疫糖尿病BALB/cByJ受体小鼠,以ICR小鼠胰岛为供体行同种异体胰岛移植。观察移植后小鼠的存活时间、移植前后外周血CD4+和CD8+T细胞亚群的变化和移植物中Th1/Th2细胞因子mRNA表达水平的变化。结果抗原特异性Treg细胞联合胰岛移植组(C组)胰岛移植物平均生存期为(34.57±17.15)d,显著长于单纯胰岛移植组(B组)的(10.6±1.82)d(P<0.01);移植后第3天,C组外周血CD4+/CD8+的值显著低于B组(P<0.01);C组移植物中IL-10,TGF-βmRNA表达比B组显著增强。B组移植物中IL-1β,IL-2及IFN-γmRNA表达明显强于C组。结论抗原特异性CD4+CD25+Treg细胞可通过调节Th2/Th1之间的反应平衡而延长同种异体胰岛移植物的存活时间。Objective To investigate the potential mechanism of antigen-specific CD4^＋ CD25^＋ regulatory T cells on the suppression of rejection for allogenetic islet transplantation in vivo. Methods Islets with 8 ×10^5 antigen-specific Treg were allogeneically transplanted under the kidney capsule of strcptozotocin-induced diabetic BALB/cByJ mice. Mean survival time （MST）, the ratio of CD4^＋/CD8^＋ T cells, cytokine expression in both tolerant and rejected mice was detected. Results In vivo, the mean survival time of recipients with islets and antigen-specific CD4^＋ CD25^＋ Treg group （ C group ） was （ 34. 57 ± 17. 15 ） days, whereas transplanted islets without Treg treatment （ B group ） survived a mean time of （ 10. 60 ± 1.82） d （ P 〈 0.01 ）. The ratio of CD4^＋/CD8^＋ T cells from antigen-specific CD4＋ CD25＋ Treg transplantation group was significantly lower than that from islet transplantation group （ P 〈 0. 01 ）. The mRNA expressions of IL-10 , TGF- were upregulated in antigen-specific CD4^＋ CD25^＋ Treg transplantation group. However, themRNA expressions of IL-1 β, IL-2, IFN-γ were similarly upregulated in islet B group. Conclusions Allogeneic antigen-specific CD4^＋ CD25^＋Treg cells can prolong islet graft survival by the mechanism of affecting Th2/Th 1 cells responses.

关 键 词：胰岛/移植 CD4^+CD25^+调节性T细胞 免疫耐受 细胞因子 

分 类 号：R617[医药卫生—外科学]