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Single-Cell Analyses Identify Dysfunctional CD16+ CD8 T Cells in Smokers

57 Pages Posted: 14 Jan 2020 Sneak Peek Status: Under Review

See all articles by Suzanne N. Martos

Suzanne N. Martos

National Institutes of Health - Environmental Epigenomics and Disease Group

Michelle R. Campbell

National Institutes of Health - Environmental Epigenomics and Disease Group

Oswaldo A. Lozoya

National Institutes of Health - Environmental Epigenomics and Disease Group

Brian D. Bennett

National Institutes of Health - Integrative Bioinformatics Support Group

Isabel Thompson

National Institutes of Health - Environmental Epigenomics and Disease Group

Ma Wan

National Institutes of Health - Environmental Epigenomics and Disease Group

Gary S. Pittman

National Institutes of Health - Environmental Epigenomics and Disease Group

Douglas A. Bell

National Institutes of Health - Environmental Epigenomics and Disease Group

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Abstract

Tobacco smoke exposure impacts immune response, leukocyte subtypes, DNA methylation, and gene expression. We performed single-cell RNA sequencing (scRNAseq) on >45,000 human peripheral blood immune cells from smokers and nonsmokers. Transcriptomes revealed a subpopulation of FCGR3A (CD16)-expressing Natural Killer (NK)-like T lymphocytes that increased in smokers. Mass cytometry confirmed an increase in the frequency of CD16+ CD8 T cells in smokers. The majority of CD16+ CD8 T cells were CD45RA positive, indicating an effector memory re-expressing CD45RA T cell (TEMRA) phenotype. Smokers’ CD8 T cells were biased toward differentiated cells and had a lower frequency of naïve cells, an indication of immune aging. FCGR3A-expressing CD8 T cells were inferred as the most differentiated cluster and expressed senescence markers. Smokers expressed senescence-linked genes in other immune populations and had elevated Tregs, which induce senescence. Our results suggest that smoking-induced, senescence-associated immune cell dysregulation contributes to smoking-mediated pathologies.

Keywords: single-cell, Mass Cytometry, Tobacco Smoke, Immune Aging, CD8 T cells, senescence, Cytolytic Potential, Dysfunctional T Cells, atherosclerosis

Suggested Citation

Martos, Suzanne N. and Campbell, Michelle R. and Lozoya, Oswaldo A. and Bennett, Brian D. and Thompson, Isabel and Wan, Ma and Pittman, Gary S. and Bell, Douglas A., Single-Cell Analyses Identify Dysfunctional CD16+ CD8 T Cells in Smokers. CR-MEDICINE-D-19-00037. Available at SSRN: https://ssrn.com/abstract=3517537 or http://dx.doi.org/10.2139/ssrn.3517537
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Suzanne N. Martos

National Institutes of Health - Environmental Epigenomics and Disease Group ( email )

United States

Michelle R. Campbell

National Institutes of Health - Environmental Epigenomics and Disease Group

United States

Oswaldo A. Lozoya

National Institutes of Health - Environmental Epigenomics and Disease Group ( email )

United States

Brian D. Bennett

National Institutes of Health - Integrative Bioinformatics Support Group

P.O. Box 12233, Mail Drop NH 06
Triangle Park, NC 27709
United States

Isabel Thompson

National Institutes of Health - Environmental Epigenomics and Disease Group ( email )

United States

Ma Wan

National Institutes of Health - Environmental Epigenomics and Disease Group ( email )

United States

Gary S. Pittman

National Institutes of Health - Environmental Epigenomics and Disease Group ( email )

United States

Douglas A. Bell (Contact Author)

National Institutes of Health - Environmental Epigenomics and Disease Group ( email )

United States

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