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肠道相关淋巴组织中树突状细胞与T细胞相互作用的差异调节

Differential regulation of dendritic cell-T cell cross talk in the gut-associated lymphoid tissue.

作者信息

Nicoletti Claudio, Temblay Jeffrey N, Regoli Mari, Bertelli Eugenio, Man Angela L

机构信息

Laboratory of Gut Immunology, Programme of GI Biology and Health, Institute of Food Research, Colney, Norwich NR4 7UA, UK.

出版信息

Mol Immunol. 2006 Feb;43(6):542-9. doi: 10.1016/j.molimm.2005.05.001. Epub 2005 Jun 13.

Abstract

Dendritic cells (DC) play a central role in the regulation of immune responses by processing and presenting antigens to naïve T cells. It has been proposed that after the initial interaction between DC and T cells, T cell-induced DC apoptosis serves as a down-regulatory mechanism that prevents the otherwise continuous activation of T cells by antigen-bearing DC. Our aim was to investigate and compare the susceptibility of Peyer's patch (PP)-derived and systemic (splenic) DC to antigen-specific T cell-mediated apoptosis in mice of different genetic background. Freshly isolated CD11c(+/hi)B220(-) DC from intestinal Peyer's patch and spleen from Balb/c and C3H/HeJ mice were co-cultured with syngeneic antigen-specific T cells in the presence or absence of the relevant antigen. In both mouse strains PP-DC showed higher susceptibility to T cell-mediated apoptosis compared to splenic ones, but levels of DC apoptosis were overall higher in C3H/HeJ mice compared to Balb/c. DC apoptosis was induced by both Th1 and Th2 antigen-specific clones and was strictly MHC class II-dependent in both strains, and interestingly we observed that although CD95-CD95L ligation played an overall minor part in T cell-induced DC apoptosis its role varied according to the mouse strain. Here, we demonstrated that PP-DC and splenic DC significantly differed in regard to their susceptibility to T cell-mediated killing. We interpreted these data as showing that the reciprocal regulation between DC and T cells in the gastrointestinal immune system is under stricter control compared to the systemic immune system and we hypothesized that these events are likely to contribute to the generation of fine balanced responses to intestinal antigens.

摘要

树突状细胞(DC)通过处理抗原并将其呈递给初始T细胞,在免疫反应调节中发挥核心作用。有人提出,在DC与T细胞的初始相互作用之后,T细胞诱导的DC凋亡作为一种下调机制,可防止携带抗原的DC持续激活T细胞。我们的目的是研究和比较不同遗传背景小鼠中派尔集合淋巴结(PP)来源的DC和全身(脾脏)DC对抗原特异性T细胞介导凋亡的敏感性。从Balb/c和C3H/HeJ小鼠的肠道派尔集合淋巴结和脾脏中新鲜分离出的CD11c(+/hi)B220(-) DC,在存在或不存在相关抗原的情况下,与同基因抗原特异性T细胞共培养。在这两种小鼠品系中,与脾脏DC相比,PP-DC对T细胞介导的凋亡表现出更高的敏感性,但与Balb/c小鼠相比,C3H/HeJ小鼠中DC凋亡水平总体上更高。Th1和Th2抗原特异性克隆均可诱导DC凋亡,并且在这两种品系中均严格依赖MHC II类分子,有趣的是,我们观察到,尽管CD95-CD95L结合在T细胞诱导的DC凋亡中总体起次要作用,但其作用因小鼠品系而异。在此,我们证明了PP-DC和脾脏DC在对T细胞介导杀伤的敏感性方面存在显著差异。我们将这些数据解释为表明,与全身免疫系统相比,胃肠道免疫系统中DC与T细胞之间的相互调节受到更严格的控制,并且我们推测这些事件可能有助于对肠道抗原产生精细平衡的反应。

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