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目的观察分析人源化NOD小鼠体内CD8+CD25+T细胞的频率及功能,探讨CD8+CD25+T细胞在人源化NOD小鼠的自身免疫进程中的作用。方法采用流式细胞术检测人源化NOD小鼠脾、胰腺引流淋巴结、腹股沟淋巴结中CD8+CD25+T、CD8+CD25+Foxp3+T细胞的频率及脾CD8+CD25+T细胞的表型和细胞因子分泌谱,并采用3H-Td R掺入法检测脾CD8+CD25+T细胞的免疫抑制功能。结果人源化NOD小鼠胰腺引流淋巴结中CD8+CD25+T和CD8+CD25+Foxp3+T细胞频率显著高于脾和腹股沟淋巴结中这2亚群的频率;与CD8+CD25-T细胞相比,脾CD8+CD25+T细胞高表达Foxp3、CTLA-4、CD103、CD62L,同时低分泌细胞因子IFN-γ及高分泌IL-17A;人源化NOD小鼠脾CD8+CD25+T细胞能有效地抑制效应性CD4+CD25-T细胞的增殖。结论人源化NOD小鼠的CD8+CD25+T细胞是一群具有免疫抑制功能的Tregs,并且高表达Tregs的表型和细胞因子谱,提示CD8+CD25+Tregs可能在外周和胰腺局部参与了人源化NOD小鼠T1D的免疫耐受进程。
Objective To investigate the frequency and function of CD8 + CD25 + T cells in humanized NOD mice and explore the role of CD8 + CD25 + T cells in autoimmunity of humanized NOD mice. Methods The frequency of CD8 + CD25 + T, CD8 + CD25 + Foxp3 + T cells in spleen, pancreas draining lymph nodes and inguinal lymph nodes of humanized NOD mice and the phenotypes of splenic CD8 + CD25 + T cells in humanized NOD mice were detected by flow cytometry Cytokine secretion profile, and 3H-Td R incorporation assay spleen CD8 CD25 T cells immunosuppressive function. Results The frequencies of CD8 + CD25 + T and CD8 + CD25 + Foxp3 + T cells in pancreatic draining lymph nodes of humanized NOD mice were significantly higher than those in the spleen and inguinal lymph nodes. Compared with CD8 + CD25-T cells , Splenic CD8 + CD25 + T cells overexpress Foxp3, CTLA-4, CD103, CD62L, while low secretion of cytokines IFN-γ and high secretion of IL-17A; humanized NOD mouse spleen CD8 + CD25 + T cells can be effective Inhibit the proliferation of effector CD4 + CD25-T cells. Conclusions CD8 + CD25 + T cells in humanized NOD mice are immunosuppressive Tregs with high expression of Tregs phenotype and cytokine profiles, suggesting that CD8 + CD25 + Tregs may be involved in the peripheral Immune tolerance of T1D-derived NOD mice.