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

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-β mRNA表达比B组显著增强。B组移植物中IL-1β，IL-2及IFN-γ mRNA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。

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

Abstract: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 8×105 antigen-specific Treg were allogeneically transplanted under the kidney capsule of streptozotocin-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-β were upregulated in antigen-specific CD4+CD25+ Treg transplantation group. However, the mRNA expressions of IL-1β, 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/Th1 cells responses.