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Sci Adv. 2019 Aug 21;5(8):eaaw8330. doi: 10.1126/sciadv.aaw8330. eCollection 2019 Aug.

Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes.

Author information

1
The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
2
Zlotowski Neuroscience Center and Regenerative Medicine and Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
3
National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
4
Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
5
Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.
6
Departments of Immunology and Neuroscience, Rappaport Faculty of Medicine, and the Integrated Cancer Center, Technion-Israel Institute of Technology, Haifa 3525422, Israel.

Abstract

Age-associated changes in CD4 T-cell functionality have been linked to chronic inflammation and decreased immunity. However, a detailed characterization of CD4 T cell phenotypes that could explain these dysregulated functional properties is lacking. We used single-cell RNA sequencing and multidimensional protein analyses to profile thousands of CD4 T cells obtained from young and old mice. We found that the landscape of CD4 T cell subsets differs markedly between young and old mice, such that three cell subsets-exhausted, cytotoxic, and activated regulatory T cells (aTregs)-appear rarely in young mice but gradually accumulate with age. Most unexpected were the extreme pro- and anti-inflammatory phenotypes of cytotoxic CD4 T cells and aTregs, respectively. These findings provide a comprehensive view of the dynamic reorganization of the CD4 T cell milieu with age and illuminate dominant subsets associated with chronic inflammation and immunity decline, suggesting new therapeutic avenues for age-related diseases.

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