T ‐cell Immunoglobulin and ITIM Domain Contributes to CD8+ T‐cell Immunosenescence

In this study, we showed that T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif (ITIM) domain (TIGIT), a novel co‐inhibitory receptor, was upregulated in CD8+ T cells of elderly adults. Aged TIGIT+ CD8+ T cells expressed high levels of other inhibitory receptors including PD‐1 and exhibited features of exhaustion such as downregulation of the key costimulatory receptor CD28, representative intrinsic transcriptional regulation, low production of cytokines, and high susceptibility to apoptosis. Importantly, their functional defects associated with aging were reversed by TIGIT knockdown. CD226 downregulation on aged TIGIT+ CD8+ T cells is likely involved in TIGIT‐mediated negative immune suppression. Collectively, our findings indicated that TIGIT acts as a critical immune regulator during aging, providing a strong rationale for targeting TIGIT to improve dysfunction related to immune system aging.

Source: Aging Cell - January 19, 2018 Category: Cytology Authors: Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Di Wang, Yuxin Li, Yu Jiang, Ling Xu, Yaluan Ma, Hong Zheng, Yaxian Kong, Hui Zeng Tags: ORIGINAL ARTICLE Source Type: research