Co-Expression of TIGIT and Helios Marks Immunosenescent CD8+ T Cells During Aging
Open Access
- 16 May 2022
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
- Vol. 13, 833531
- https://doi.org/10.3389/fimmu.2022.833531
Abstract
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.Funding Information
- Ministerie van Volksgezondheid, Welzijn en Sport
This publication has 47 references indexed in Scilit:
- Reversal of functional defects in highly differentiated young and old CD8 T cells by PDL blockadeImmunology, 2012
- Are senescence and exhaustion intertwined or unrelated processes that compromise immunity?Nature Reviews Immunology, 2011
- CD28− T cells: their role in the age-associated decline of immune functionTrends in Immunology, 2009
- KLRG1 signaling induces defective Akt (ser473) phosphorylation and proliferative dysfunction of highly differentiated CD8+ T cellsBlood, 2009
- Mortality Associated With Influenza and Respiratory Syncytial Virus in the United StatesJAMA, 2003
- Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infectionsNature Medicine, 2002
- Age-related impairment of human T lymphocytes’ activation: specific differences between CD4+ and CD8+ subsetsMechanisms of Ageing and Development, 2002
- In vitro T cell activation in elderly individuals: failure in CD69 and CD71 expressionMechanisms of Ageing and Development, 1996
- Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2Nature, 1987
- Cytotoxic T-Cell Immunity to InfluenzaThe New England Journal of Medicine, 1983