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

  • Cell Rep. 2019 Jul 30;28(5):1127-1135.e4. doi: 10.1016/j.celrep.2019.06.087.
Elizabeth A Thompson  1 ,  Patricia A Darrah  2 ,  Kathryn E Foulds  2 ,  Elena Hoffer  3 ,  Alayna Caffrey-Carr  4 ,  Sophie Norenstedt  5 ,  Leif Perbeck  6 ,  Robert A Seder  2 ,  Ross M Kedl  4 ,  Karin Loré  7
Affiliations
  • 1. Department of Medicine, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm 17164, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden. Electronic address: [email protected].
  • 2. Vaccine Research Center, NIAID, NIH, Bethesda, MD 20892, USA.
  • 3. Department of Medicine, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm 17164, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden.
  • 4. Department of Immunology & Microbiology, University of Colorado Denver, Aurora, CO 80045, USA.
  • 5. Kirurgkliniken, Capio St Görans Sjukhus, Stockholm 11281, Sweden.
  • 6. Department of Surgery, Karolinska University Hospital, Solna 17176, Sweden.
  • 7. Department of Medicine, Division of Immunology and Allergy, Karolinska Institutet and Karolinska University Hospital, Stockholm 17164, Sweden; Center for Molecular Medicine, Karolinska Institutet, Stockholm 17176, Sweden. Electronic address: [email protected].
PMID: 31365858 DOI: 10.1016/j.celrep.2019.06.087
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.

Keywords
IL-10; T cell; TGF-beta; TRM; anti-CD40; monocyte; non-human primate; tissue-resident memory T cells; toll-like receptor; vaccine.
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