Open AccessIL-21 from high-affinity CD4 T cells drives differentiation of brain-resident CD8 T cells during persistent viral infection
Author(s) -
Heather M. Ren,
Elizabeth Motunrayo Kolawole,
Mingqiang Ren,
Ge Jin,
Colleen S. Netherby,
Quinn Wade,
.. Shwetank,
Ziaur S. M. Rahman,
Brian D. Evavold,
Aron E. Lukacher
Publication year - 2020
Publication title -
science immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.83
H-Index - 51
ISSN - 2470-9468
DOI - 10.1126/sciimmunol.abb5590
Subject(s) - cytotoxic t cell , biology , cd8 , interleukin 21 , t cell receptor , t cell , il 2 receptor , zap70 , cd28 , natural killer t cell , interleukin 3 , receptor , microbiology and biotechnology , immunology , antigen , immune system , biochemistry , in vitro
Development of tissue-resident memory (T RM ) CD8 T cells depends on CD4 T cells. In polyomavirus central nervous system infection, brain CXCR5 hi PD-1 hi CD4 T cells produce interleukin-21 (IL-21), and CD8 T cells lacking IL-21 receptors (IL21R -/- ) fail to become bT RM 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 T RM 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 CXCR5 hi PD-1 hi CD4 T cells in the brain produce IL-21, which drives CD8 bT RM differentiation in response to a persistent viral infection.