Open AccessT‐cell Immunoglobulin and ITIM Domain Contributes to CD 8 + T‐cell Immunosenescence
Author(s) -
Song Yangzi,
Wang Beibei,
Song Rui,
Hao Yu,
Wang Di,
Li Yuxin,
Jiang Yu,
Xu Ling,
Ma Yaluan,
Zheng Hong,
Kong Yaxian,
Zeng Hui
Publication year - 2018
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12716
Subject(s) - tigit , immunosenescence , downregulation and upregulation , biology , immune system , cd8 , cytotoxic t cell , t cell , immune receptor , cd28 , microbiology and biotechnology , receptor , immunology , cancer research , biochemistry , gene , in vitro
Summary Aging is associated with immune dysfunction, especially T‐cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T‐cell exhaustion and T‐cell senescence. 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 CD 8 + T cells of elderly adults. Aged TIGIT + CD 8 + 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 CD 28, 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. CD 226 downregulation on aged TIGIT + CD 8 + 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.