1. Single-cell analyses identify dysfunctional CD16 + CD8 T cells in smokers.
- Author
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Martos SN, Campbell MR, Lozoya OA, Wang X, Bennett BD, Thompson IJB, Wan M, Pittman GS, and Bell DA
- Subjects
- Adult, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cigarette Smoking immunology, Female, GPI-Linked Proteins drug effects, GPI-Linked Proteins immunology, GPI-Linked Proteins metabolism, Humans, Immune System Diseases physiopathology, Killer Cells, Natural immunology, Leukocyte Common Antigens, Male, Middle Aged, Receptors, IgG drug effects, Receptors, IgG immunology, Single-Cell Analysis methods, Smokers, Smoking blood, CD8-Positive T-Lymphocytes drug effects, Cigarette Smoking adverse effects, Receptors, IgG metabolism
- Abstract
Tobacco smoke exposure contributes to the global burden of communicable and chronic diseases. To identify immune cells affected by smoking, we use single-cell RNA sequencing on peripheral blood from smokers and nonsmokers. Transcriptomes reveal a subpopulation of FCGR3A (CD16)-expressing Natural Killer (NK)-like CD8 T lymphocytes that increase in smokers. Mass cytometry confirms elevated CD16
+ CD8 T cells in smokers. Inferred as highly differentiated by pseudotime analysis, NK-like CD8 T cells express markers characteristic of effector memory re-expressing CD45RA T (TEMRA ) cells. Indicative of immune aging, smokers' CD8 T cells are biased toward differentiated cells and smokers have fewer naïve cells than nonsmokers. DNA methylation-based models show that smoking dose is associated with accelerated aging and decreased telomere length, a biomarker of T cell senescence. Immune aging accompanies T cell senescence, which can ultimately lead to impaired immune function. This suggests a role for smoking-induced, senescence-associated immune dysregulation in smoking-mediated pathologies., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.- Published
- 2020
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