同种异体反应性细胞与调节性T细胞在新生期诱导的小鼠移植耐受中的作用探讨

发布时间：2018-03-28 03:28

本文选题：同种异体反应性T细胞　切入点：调节性T细胞　出处：《中国免疫学杂志》2015年01期

【摘要】：目的:初步探讨同种异体反应性T细胞克隆清除与调节性T细胞在小鼠移植耐受中的作用。方法:雌性BALB/c小鼠与雄性C57BL/6小鼠杂交一代获得F1小鼠,不同剂量的F1小鼠脾脏细胞经眶静脉输注给新生24 h C57BL/6小鼠体内诱导耐受,成年后移植F1小鼠来源的皮肤,建立不同耐受程度的小鼠移植耐受模型;耐受小鼠脾脏细胞经CFSE标记后注射到F1小鼠体内,分析耐受小鼠来源的T细胞在体内对F1抗原的增殖能力;流式细胞术、过继转移实验分析CD4+Foxp3+调节性T细胞在移植耐受和移植排斥过程中的表达。结果:C57BL/6小鼠在新生期输注F1小鼠脾脏细胞可诱导移植耐受,耐受程度与输注的脾脏细胞剂量有关,3×107个F1小鼠脾脏细胞可诱导C57BL/76小鼠长期皮肤移植耐受,1×107个细胞诱导可使移植皮肤生存时间显著延长,但在50 d内完全排斥;体内混合淋巴细胞反应实验证明,长期耐受小鼠体内的同种异体反应性T细胞被完全克隆清除,但低剂量组小鼠体内仍存在一定数量的反应性T细胞;流式细胞分析发现,高剂量和低剂量组小鼠体内的CD4+Foxp3+调节性T细胞表达与初始小鼠相比没有显著差异;同种异体反应性T细胞过继转移给耐受小鼠,移植耐受的皮肤发生排斥反应,小鼠体内的调节性T细胞表达升高。结论:小鼠的移植耐受程度与小鼠体内的同种异体反应性T细胞的克隆清除程度有关,与CD4+Foxp3+调节性T细胞的表达没有直接关系;调节细胞在移植排斥过程中表达升高,可能作为一种反馈机制参与耐受的形成。
[Abstract]:Objective: to investigate the role of allogeneic reactive T cell clone clearance and regulatory T cell in transplantation tolerance in mice. Methods: F1 mice were obtained by hybridization between female BALB/c mice and male C57BL/6 mice. Different doses of spleen cells of F1 mice were infused via orbital vein to induce tolerance in newborn C57BL/6 mice for 24 h. The skin derived from F1 mice was transplanted into adult mice to establish mice model of transplantation tolerance with different degrees of tolerance. The spleen cells of tolerant mice were injected into F1 mice by CFSE labeling, and the proliferative ability of T cells derived from tolerant mice to F1 antigen was analyzed. Adoptive transfer assay was used to analyze the expression of CD4 Foxp3 regulatory T cells in the process of transplantation tolerance and rejection. The degree of tolerance was related to the amount of splenic cells injected into C57BL/76 mice. The spleen cells of 3 脳 107 F1 mice could induce long-term skin transplantation tolerance in C57BL/76 mice. The induction of 1 脳 107 cells could prolong the survival time of transplanted skin significantly, but completely reject the transplanted skin within 50 days. In vivo mixed lymphocyte reaction assay showed that allogeneic reactive T cells were completely cloned and eliminated in long-term tolerant mice, but there were still a certain number of reactive T cells in low dose group. There was no significant difference in the expression of CD4 Foxp3 regulatory T cells between the high and low dose groups compared with the original mice. Conclusion: the degree of transplantation tolerance is related to the clonal clearance of allogeneic reactive T cells in mice, but not to the expression of CD4 Foxp3 regulatory T cells. Regulation of increased expression of cells during transplant rejection may be a feedback mechanism involved in the formation of tolerance.
【作者单位】：郑州大学第一附属医院检验科河南省检验医学重点实验室;
【基金】：国家自然科学基金项目(81172835)
【分类号】：R392.4

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