Activation of Human Mucosal-Associated Invariant T Cells Induces CD40L-Dependent Maturation of Monocyte-Derived and Primary Dendritic Cells

J Immunol. 2017 Oct 15;199(8):2631-2638. doi: 10.4049/jimmunol.1700615. Epub 2017 Sep 6.

Abstract

Mucosal-associated invariant T (MAIT) cells are innate T cells that recognize intermediates of the vitamin B2 biosynthetic pathway presented by the monomorphic MR1 molecule. It remains unclear whether, in addition to their cytolytic activity that is important in antimicrobial defense, MAIT cells have immune-modulatory functions that could enhance dendritic cell (DC) maturation. In this study, we investigated the molecular mechanisms dictating the interactions between human MAIT cells and DCs and demonstrate that human MAIT cells mature monocyte-derived and primary DCs in an MR1- and CD40L-dependent manner. Furthermore, we show that MAIT cell-derived signals synergize with microbial stimuli to induce secretion of bioactive IL-12 by DCs. Activation of human MAIT cells in whole blood leads to MR1- and cytokine-dependent NK cell transactivation. Our results underscore an important property of MAIT cells, which can be of translational relevance to rapidly orchestrate adaptive immunity through DC maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD40 Ligand / metabolism
  • Cell Communication
  • Cell Differentiation
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immunity, Mucosal
  • Interleukin-12 / metabolism
  • Lymphocyte Activation*
  • Minor Histocompatibility Antigens / metabolism
  • Monocytes / immunology
  • Natural Killer T-Cells / immunology*
  • Receptor Cross-Talk
  • Riboflavin / immunology
  • Riboflavin / metabolism
  • Signal Transduction

Substances

  • Histocompatibility Antigens Class I
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • CD40 Ligand
  • Interleukin-12
  • Riboflavin