The cell-surface 5'-nucleotidase CD73 defines a functional T memory cell subset that declines with age

Cell Rep. 2021 Nov 9;37(6):109981. doi: 10.1016/j.celrep.2021.109981.

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-5'-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.

Keywords: CD73; RUNX; T cell differentiation; adenosine; aging; heterogeneity; immunosenescence; memory T cell; tissue-residing memory T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 5'-Nucleotidase / genetics
  • 5'-Nucleotidase / metabolism*
  • Adult
  • Age Factors
  • Aged
  • Animals
  • Cell Differentiation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Immunologic Memory*
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • T-Lymphocyte Subsets / immunology*

Substances

  • 5'-Nucleotidase