TNF type 2 receptor (p75) lowers the threshold of T cell activation
TNF type 2 receptor (p75) lowers the threshold of T cell activation
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DOI：
10.4049/jimmunol.167.12.6812
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发表时间：
2001-12-15
影响因子：
4.4
通讯作者：
Teh, HS
中科院分区：
文献类型：
--
作者：
Kim, EY;Teh, HS
T细胞活化需要阈值量的TCR介导的信号，该量被通过T细胞表面上表达的共刺激分子介导的信号减少。在这里，TNFR 2（p75）作为一个假定的T细胞活化的共刺激受体的作用进行了检查。发现CD 8（+）T细胞中的p75缺陷使对TCR激动剂的需求增加约5倍。此外，p75（-/-）T细胞显示对TCR激动剂的增殖应答显著降低。这种低增殖反应与急性活化标志物CD 25和CD 69诱导的延迟动力学以及IL-2和IFN-γ产生的显著减少相关。最终的结果是很少的细胞被招募到分裂的群体中。有趣的是，CD 28共刺激在挽救p75（-/-）CD 8（+）T细胞的增殖缺陷方面仅部分有效。因此，除了CD 28提供的信号外，p75还提供了重要的共刺激信号，以促进最佳T细胞增殖。
T cell activation requires a threshold amount of TCR-mediated signals, an amount that is reduced by signals mediated through costimulatory molecules expressed on the T cell surface. Here the role of TNFR2 (p75) as a putative costimulatory receptor for T cell activation was examined. It was found that p75 deficiency in CD8(+) T cells increased the requirements for TCR agonist approximately 5-fold. Furthermore, p75(-/-) T cells display a marked reduction in the proliferative response to TCR agonist. This hypoproliferative response was associated with delayed kinetics of induction of the acute activation markers CD25 and CD69 as well as a marked decrease in the production of IL-2 and IFN-gamma. The net result is that very few cells are recruited into the dividing population. Interestingly, CD28 costimulation was only partially effective in rescuing the proliferative defect of p75(-/-)CD8(+) T cells. Thus, p75 provides an important costimulatory signal in addition to that provided by CD28 toward optimal T cell proliferation.