The cell-surface 5′-nucleotidase CD73 defines a functional T memory cell subset that declines with age

Fengqin Fang, Wenqiang Cao, Weikang Zhu, Nora Lam, Lingjie Li, Sadhana Gaddam, Yong Wang, Chulwoo Kim, Simon Lambert, Huimin Zhang, Bin Hu, Donna L. Farber, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

Abstract

Memory T cells exhibit considerable diversity that determines their ability to be protective. Here, we examine whether changes in T cell heterogeneity contribute to the age-associated failure of immune memory. By screening for age-dependent T cell-surface markers, we identify CD4 and CD8 memory T cell subsets that are unrelated to previously defined subsets of central and effector memory cells. Memory T cells expressing the ecto-5ʹ-nucleotidase CD73 constitute a functionally distinct subset of memory T cells that declines with age. They resemble long-lived, polyfunctional memory cells but are also poised to display effector functions and to develop into cells resembling tissue-resident memory T cells (TRMs). Upstream regulators of differential chromatin accessibility and transcriptomes include transcription factors that facilitate CD73 expression and regulate TRM differentiation. CD73 is not just a surrogate marker of these regulatory networks but is directly involved in T cell survival.

Original languageEnglish (US)
Article number109981
JournalCell reports
Volume37
Issue number6
DOIs
StatePublished - Nov 9 2021

Keywords

  • adenosine
  • aging
  • CD73
  • heterogeneity
  • immunosenescence
  • memory T cell
  • RUNX
  • T cell differentiation
  • tissue-residing memory T cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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