Co-Expression of TIGIT and Helios Marks Immunosenescent CD8 + T Cells During Aging.

Autor:	Pieren DKJ; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands., Smits NAM; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands., Postel RJ; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands., Kandiah V; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands., de Wit J; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands., van Beek J; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands., van Baarle D; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Guichelaar T; Centre for Infectious Disease Control, National Institute for Public Health and The Environment, Bilthoven, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 May 16; Vol. 13, pp. 833531. Date of Electronic Publication: 2022 May 16 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.833531
Abstrakt:	Aging leads to alterations in the immune system that result in ineffective responsiveness against pathogens. Features of this process, collectively known as immunosenescence, accumulate in CD8 + T cells with age and have been ascribed to differentiation of these cells during the course of life. Here we aimed to identify novel markers in CD8 + T cells associated with immunosenescence. Furthermore, we assessed how these markers relate to the aging-related accumulation of highly differentiated CD27 - CD28 - cells. We found that co-expression of the transcription factor Helios and the aging-related marker TIGIT identifies CD8 + T cells that fail to proliferate and show impaired induction of activation markers CD69 and CD25 in response to stimulation in vitro . Despite this, in blood of older adults we found TIGIT + Helios + T cells to become highly activated during an influenza-A virus infection, but these higher frequencies of activated TIGIT + Helios + T cells associate with longer duration of coughing. Moreover, in healthy individuals, we found that TIGIT + Helios + CD8 + T cells accumulate with age in the highly differentiated CD27 - CD28 - population. Interestingly, TIGIT + Helios + CD8 + T cells also accumulate with age among the less differentiated CD27 + CD28 - T cells before their transit into the highly differentiated CD27 - CD28 - stage. This finding suggests that T cells with immunosenescent features become prominent at old age also within the earlier differentiation states of these cells. Our findings show that co-expression of TIGIT and Helios refines the definition of immunosenescent CD8 + T cells and challenge the current dogma of late differentiation stage as proxy for T-cell immunosenescence. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Pieren, Smits, Postel, Kandiah, de Wit, van Beek, van Baarle and Guichelaar.)
Databáze:	MEDLINE
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