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

Yehezqel Elyahu, Idan Hekselman, Inbal Eizenberg-Magar, Omer Berner, Itai Strominger, Maya Schiller, Kritika Mittal, Anna Nemirovsky, Ekaterina Eremenko, Assaf Vital, Eyal Simonovsky, Vered Chalifa-Caspi, Nir Friedman, Esti Yeger-Lotem, Alon Monsonego

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish
Article numbereaaw8330
JournalScience advances
Volume5
Issue number8
DOIs
StatePublished - 21 Aug 2019

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