小鼠γδT细胞免疫调节表型的初步研究

发布时间：2018-01-13 13:12

本文关键词：小鼠γδT细胞免疫调节表型的初步研究　出处：《中国协和医科大学》2008年硕士论文　论文类型：学位论文

【摘要】： 调节性T细胞(Regulatory T cell，Treg)作为T细胞的一个亚群已被明确定义为能够抑制自身反应性T细胞的活性和增殖，维持机体免疫耐受的一类细胞。由于其来源和功能不同，可以将Treg分为很多类型，如经典CD4~+CD25~+Treg，以及新近所关注的CD8~+Treg、NK Treg和γδTreg。目前研究最为深入的为CD4~+CD25~+Treg，这类细胞高表达Foxp3(Forkhead/winged-helix familytranscriptional repressor p3)，而Foxp3被认为是Treg细胞最特异的标志物，是CD4~+CD25~+Treg细胞的主要控制基因。为了研究γδT细胞中是否也具有免疫调节表型的细胞亚群，我们以小鼠为研究体系，对脾脏来源的淋巴细胞、肠道上皮内淋巴细胞(Intraepitheliallymphocyte，IEL)和胸腺来源的淋巴细胞中γδT细胞进行了研究。我们发现，在新鲜分离的γδT细胞中的确存在Foxp3~+亚群，尤其在经过TGF-β体外诱导后，这类亚群比例明显增加。与此同时，TGF-β诱导后的γδT细胞，其与免疫调节相关的其他表型和细胞因子也有明显变化，其中IL-10、GITR、CTLA-4、TLR-8、CCR2和TGF-β等表达增加，而INF-γ表达降低。而利用IL-10对γδT细胞进行体外诱导并不会出现Foxp3表达的进一步增高；TGF-β与IL-6共刺激γδT细胞时也并不能促进IL-17的表达。以上结果提示小鼠Foxp3~+γδT细胞可以经过TGF-β进行体外诱导，出现类似于CD4~+CD25~+T细胞的表型；但小鼠γδT细胞不能在体外诱导出Tr1或TH17样表型。另外，我们还利用黑色素瘤小鼠模型对γδT细胞在肿瘤免疫中的作用进行了初步研究。我们的研究结果表明Foxp3~+γδT细胞在肿瘤浸润淋巴细胞(Tumorinfiltrating lymphocyte,TIL)和肠道IEL中所占的比例随肿瘤的增长有所增加，，提示Foxp3~+γδT细胞可能与肿瘤的免疫抑制有关。综上，本文初步研究了小鼠Foxp3~+γδT细胞的表型与功能，验证了具有免疫调节表型的γδT细胞的存在，为调节性γδT的进一步研究提供了线索和基础。
[Abstract]:Regulatory T cells (Regulatory T cell, Treg) as a subgroup of T cells has been clearly defined as capable of inhibiting the activation and proliferation of autoreactive T cells maintain a cell immune tolerance. Because of its origin and different functions, Treg can be divided into many types, such as the classic CD4~+CD25~+Treg. And the new CD8~+Treg concern, NK Treg and gamma delta Treg. currently the most in-depth study of the CD4~+CD25~+Treg, the high expression of Foxp3 cells (Forkhead/winged-helix familytranscriptional repressor P3), and Foxp3 is considered to be the most specific markers of Treg cells, is the main control genes in CD4~+CD25~+Treg cells.
In order to study the gamma delta T cells also have immunomodulatory phenotype cells in mice, we study on the system, the source of spleen lymphocytes and intestinal intraepithelial lymphocytes (Intraepitheliallymphocyte, IEL) and thymus derived lymphocytes in T cells were studied. We found that in freshly isolated gamma delta T cells do exist Foxp3~+ subsets, especially after the induction of TGF- in vitro, such subsets increased significantly. At the same time, TGF- beta induced gamma delta T cells, and the immune phenotype and other related cytokines also have obvious changes, including IL-10, GITR, CTLA-4, TLR-8, CCR2 and the TGF- beta expression increased, while INF- decreased. And the use of IL-10 gamma expression of gamma delta T cells were further increased in vitro and not Foxp3 expression; TGF- and IL-6 costimulatory beta gamma delta T cells also did not promote IL-17. These results suggest that Foxp3~+ gamma delta T cells can be induced by TGF- beta in vitro, and appear phenotypes similar to CD4~+CD25~+T cells, but mouse gamma delta T cells can not induce Tr1 or TH17 like phenotype in vitro.
In addition, we also use the model of melanoma in mice of gamma delta T cells in tumor immunity were studied. The results of our study showed that Foxp3~+ T cells in tumor infiltrating lymphocytes (Tumorinfiltrating, lymphocyte, TIL) and the proportion of intestinal IEL with tumor growth increased, suggesting that Foxp3~+ gamma delta T cells may be related to tumor immune suppression.
In conclusion, the phenotype and function of mouse Foxp3~+ gamma delta T cells were preliminarily studied, and the existence of gamma delta T cells with immunomodulatory phenotype was verified, which provided clues and basis for further research of regulatory gamma delta T.

【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R392

【相似文献】