Monocytes Acquire the Ability to Prime Tissue-Resident T Cells via IL-10-Mediated TGF-β Release

Cell Reports
Elizabeth A ThompsonKarin Loré

Abstract

Using non-human primates (NHPs), mice, and human primary cells, we found a role for interleukin-10 (IL-10) in the upregulation of the tissue-resident memory T cell (TRM) marker CD103. In NHPs, intravenous, but not subcutaneous, immunization with peptide antigen and an adjuvant combining an agonistic anti-CD40 antibody plus poly(IC:LC) induced high levels of CD103+ TRMs in the lung, which correlated with early plasma IL-10 levels. Blocking IL-10 reduced CD103 expression on human T cells stimulated in vitro with the adjuvant combination as well as diminished CD103 on lung-resident T cells in vivo in mice. Monocyte-produced IL-10 induced the release of surface-bound transforming growth factor β (TGF-β), which in turn upregulated CD103 on T cells. Early TGF-β imprinted increased sensitivity to TGF-β restimulation, indicating an early commitment of the T cell lineage toward TRMs during the priming stage of activation. IL-10-mediated TGF-β signaling may therefore have a critical role in the generation of TRM following vaccination.

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Citations

Apr 25, 2020·American Journal of Reproductive Immunology : AJRI·Xixi HuangMeirong Du
Jan 23, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kuan-Lun ChuTania H Watts
Sep 16, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jingya XiaSusan L Swain
Dec 10, 2020·Microorganisms·Erin I ArmentroutGislâine A Martins
Apr 22, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samira MansouriLei Jin
Dec 12, 2020·American Journal of Respiratory and Critical Care Medicine·Mark E SnyderPablo Sanchez
May 18, 2021·Advanced Therapeutics·Frances C Knight, John T Wilson
May 7, 2021·Journal of Virology·Woojong LeeM Suresh
Mar 24, 2021·Cold Spring Harbor Perspectives in Biology·Simone L Park, Laura K Mackay

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Methods Mentioned

BETA
bronchoalveolar lavage
flow cytometry
FACS
Assay
ELISA

Software Mentioned

GraphPad Prism

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