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

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 ? (TGF-?), which in turn upregulated CD103 on T cells. Early TGF-? imprinted increased sensitivity to TGF-? restimulation, indicating an early commitment of the T cell lineage toward TRMs during the priming stage of activation. IL-10-mediated TGF-? signaling may therefore have a critical role in the generation of TRM following vaccination.

SUBMITTER: Thompson EA 

PROVIDER: S-EPMC6825402 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature