期刊
CELLS
卷 10, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/cells10020418
关键词
regulatory T cell; tolerance; immunological synapse; central supramolecular activation cluster (cSMAC); supramolecular signaling complex; linker for activation of T cells (LAT); inhibitory receptors; CTLA-4; PD-1
类别
资金
- Wellcome Trust [102387/Z/13/Z]
- European Research Council [PCIG11-GA-2012-321554]
- UCB
- AstraZeneca
- U.S. National Institutes of Health [GM103712]
- Wellcome Trust [102387/Z/13/Z] Funding Source: Wellcome Trust
Peripheral immune regulation is crucial for self-tolerance maintenance. Investigating signaling processes in T cells revealed distinct features between regulatory T cells and effector T cells. Regulatory T cells exhibit more rapid termination of signaling, possibly influenced by attenuation of proximal signaling.
Peripheral immune regulation is critical for the maintenance of self-tolerance. Here we have investigated signaling processes that distinguish T cells with regulatory capability from effector T cells. The murine Tg4 T cell receptor recognizes a peptide derived from the self-antigen myelin basic protein. T cells from Tg4 T cell receptor transgenic mice can be used to generate effector T cells and three types of T cells with regulatory capability, inducible regulatory T cells, T cells tolerized by repeated in vivo antigenic peptide exposure or T cells treated with the tolerogenic drug UCB9608 (a phosphatidylinositol 4 kinase III beta inhibitor). We comparatively studied signaling in all of these T cells by activating them with the same antigen presenting cells presenting the same myelin basic protein peptide. Supramolecular signaling structures, as efficiently detected by large-scale live cell imaging, are critical mediators of T cell activation. The formation of a supramolecular signaling complex anchored by the adaptor protein linker for activation of T cells (LAT) was consistently terminated more rapidly in Tg4 T cells with regulatory capability. Such termination could be partially reversed by blocking the inhibitory receptors CTLA-4 and PD-1. Our work suggests that attenuation of proximal signaling may favor regulatory over effector function in T cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据