新型记忆性CD4T细胞亚群负向调控树突状细胞成熟和功能及其机制研究
发布时间：2018-12-27 08:08
【摘要】：免疫记忆是免疫系统的一大特征,少量的记忆性细胞便能对再次免疫应答产生显著的影响,但其发挥作用的机制并不十分清楚。树突状细胞(DCs)是专职性抗原提呈细胞,DC的功能状态以及不同的DC亚群对特异性免疫细胞的分化方向和反应强度起到决定性的作用,在激发免疫应答和诱导免疫耐受中均发挥着关键作用。目前发现,DC对于不同的T细胞亚群包括免疫记忆性T细胞的形成具有重要作用。记忆性CD4T细胞由于其数量稀少难以获得,所以对于记忆性CD4T细胞与其它免疫细胞亚群的相互作用的研究比较少,其中,记忆性CD4T细胞对DC具体功能的调控和机制仍不完全清楚。 我们在前期研究中发现调节性DC可诱导产生一群高分泌IL-4/IL-10的记忆性Th2细胞(命名为Tm2),Tm2可通过IL-10抑制成熟DC诱导的CD4T细胞增殖；同时建立了能够大量制备该记忆性细胞亚群的体外培养体系以便于开展功能研究。在本研究中,我们深入研究了Tm2对DC功能的直接调控作用及其相关机制。我们发现,Tm2能够抑制DC表面共刺激分子CD80和CD86的表达,抑制其IL-6、IL-1β和IL-12p70的表达,使得DC促进初始T细胞增殖和活化的能力下降。Tm2对DC的这种效应依赖于抗原特异性的活化,并且依赖于活化后IL-10和IL-4的分泌。而且在体内,Tm2也能抑制免疫状态下淋巴结中DC表面CD86的表达。本研究结果提示,记忆性CD4T细胞可以通过改变DC的功能状态,发挥并且放大其免疫抑制效应,参与调控再次免疫应答的效应。本研究进一步深化了对记忆性T细胞发挥作用机制的认识,并深入认识DC在再次免疫应答中受到记忆性CD4T细胞亚群的精细调控,为疫苗的设计和应用提供了理论基础。
[Abstract]:Immune memory is a major feature of the immune system, a small number of memory cells can have a significant impact on the re-immune response, but the mechanism of its role is not very clear. Dendritic cells (DCs) are specialized antigen presenting cells. The functional status of DC and different DC subsets play a decisive role in the differentiation direction and response intensity of specific immune cells. It plays a key role in stimulating immune response and inducing immune tolerance. It has been found that DC plays an important role in the formation of different T cell subsets, including immune memory T cells. Because the number of memory CD4T cells is scarce and difficult to obtain, the interaction between memory CD4T cells and other immune cell subsets is less studied. Among them, the regulation and mechanism of memory CD4T cells on the specific function of DC are still unclear. In previous studies, we found that regulatory DC could induce the production of a group of memory Th2 cells (named Tm2) with high secretion of IL-4/IL-10, and Tm2 could inhibit the proliferation of CD4T cells induced by mature DC through IL-10. At the same time, an in vitro culture system was established to prepare the memory cell subsets in large quantities for the purpose of functional study. In this study, we studied the direct regulation of DC function by Tm2 and its related mechanisms. We found that Tm2 could inhibit the expression of CD80 and CD86, IL-6,IL-1 尾 and IL-12p70 on the surface of DC. The ability of DC to promote the proliferation and activation of primary T cells was decreased. This effect of Tm2 on DC was dependent on antigen-specific activation and on the secretion of IL-10 and IL-4 after activation. In vivo, Tm2 can also inhibit the expression of CD86 on DC surface in immune lymph nodes. Our results suggest that memory CD4T cells can play and amplify the immunosuppressive effect of DC by changing the functional state of DC, and participate in the regulation of reimmune response. This study has further deepened the understanding of the mechanism of memory T cells and the fine regulation of DC by memory CD4T cell subsets in the reimmune response, which provides a theoretical basis for the design and application of vaccines.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R392
本文编号：2392754
[Abstract]:Immune memory is a major feature of the immune system, a small number of memory cells can have a significant impact on the re-immune response, but the mechanism of its role is not very clear. Dendritic cells (DCs) are specialized antigen presenting cells. The functional status of DC and different DC subsets play a decisive role in the differentiation direction and response intensity of specific immune cells. It plays a key role in stimulating immune response and inducing immune tolerance. It has been found that DC plays an important role in the formation of different T cell subsets, including immune memory T cells. Because the number of memory CD4T cells is scarce and difficult to obtain, the interaction between memory CD4T cells and other immune cell subsets is less studied. Among them, the regulation and mechanism of memory CD4T cells on the specific function of DC are still unclear. In previous studies, we found that regulatory DC could induce the production of a group of memory Th2 cells (named Tm2) with high secretion of IL-4/IL-10, and Tm2 could inhibit the proliferation of CD4T cells induced by mature DC through IL-10. At the same time, an in vitro culture system was established to prepare the memory cell subsets in large quantities for the purpose of functional study. In this study, we studied the direct regulation of DC function by Tm2 and its related mechanisms. We found that Tm2 could inhibit the expression of CD80 and CD86, IL-6,IL-1 尾 and IL-12p70 on the surface of DC. The ability of DC to promote the proliferation and activation of primary T cells was decreased. This effect of Tm2 on DC was dependent on antigen-specific activation and on the secretion of IL-10 and IL-4 after activation. In vivo, Tm2 can also inhibit the expression of CD86 on DC surface in immune lymph nodes. Our results suggest that memory CD4T cells can play and amplify the immunosuppressive effect of DC by changing the functional state of DC, and participate in the regulation of reimmune response. This study has further deepened the understanding of the mechanism of memory T cells and the fine regulation of DC by memory CD4T cell subsets in the reimmune response, which provides a theoretical basis for the design and application of vaccines.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R392
【共引文献】
相关博士学位论文 前1条
1 吕进;甲型流感病毒（H1N1）感染介导的小鼠肺免疫损伤机制研究[D];中国人民解放军军事医学科学院;2010年
相关硕士学位论文 前1条
1 卢红娟;体外建立CD4~+记忆性T细胞生成模型和分子机制的初探[D];第二军医大学;2011年
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