IL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection

Heather M. Ren, Elizabeth M. Kolawole, Mingqiang Ren, Ge Jin, Colleen S. Netherby-Winslow, Quinn Wade, Shwetank, Ziaur S.M. Rahman, Brian D. Evavold, Aron E. Lukacher

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Development of tissue-resident memory (TRM) CD8 T cells depends on CD4 T cells. In polyomavirus central nervous system infection, brain CXCR5hi PD-1hi CD4 T cells produce interleukin-21 (IL-21), and CD8 T cells lacking IL-21 receptors (IL21R−/−) fail to become bTRM. IL-21+ CD4 T cells exhibit elevated T cell receptor (TCR) affinity and higher TCR density. IL21R−/− brain CD8 T cells do not express CD103, depend on vascular CD8 T cells for maintenance, are antigen recall defective, and lack TRM core signature genes. CD4 T cell-deficient and IL21R−/− brain CD8 T cells show similar deficiencies in expression of genes for oxidative metabolism, and intrathecal delivery of IL-21 to CD4 T cell-depleted mice restores expression of electron transport genes in CD8 T cells to wild-type levels. Thus, high-affinity CXCR5hi PD-1hi CD4 T cells in the brain produce IL-21, which drives CD8 bTRM differentiation in response to a persistent viral infection.

Original languageEnglish (US)
Article numberA1
JournalScience Immunology
Volume5
Issue number51
DOIs
StatePublished - Sep 2020

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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