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

T‐cell Immunoglobulin and ITIM Domain Contributes to CD8+ T‐cell Immunosenescence 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 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Aging Cell Wiley

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

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
Copyright © 2018 The Anatomical Society and John Wiley & Sons Ltd.
ISSN
1474-9718
eISSN
1474-9726
D.O.I.
10.1111/acel.12716
Publisher site
See Article on Publisher Site

Abstract

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 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.

Journal

Aging CellWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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