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

Mariolina Salio,Jacob G Verter,Ian F Hermans,Giorgio Napolitani,Claudia Gonzalez-Lopez,Vincenzo Cerundolo,Olivier Gasser,Gavin Painter,Regan Anderson,Natacha Veerapen,Gurdyal S Besra,Uzi Gileadi,Anne Martens

doi:10.4049/jimmunol.1700615

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.

Highlights

In this article we have demonstrated that human Mucosal-associated invariant T (MAIT) cells rapidly upregulate CD40L upon activation by the cognate Ag 5-A-RU/ MG presented by the nonclassical class I molecule MR1
We have shown that MAIT cells are able to instruct dendritic cell (DC) maturation in a CD40L- and MR1-dependent manner, resulting in secretion of bioactive IL-12
We have demonstrated that, upon Ag-specific activation, MAIT cells rapidly upregulate CD40L at the cell surface and, in synergy with TLR ligands, induce secretion of bioactive IL-12 by DCs

Summary

Introduction

The specificity of MAIT cell activation was demonstrated with anti-MR1 Abs, which blocked CD40L expression and TNF-a secretion (Fig. 1B). MAIT cells enhanced maturation induced by supernatant of DH5a E. coli (Fig. 2B, 2C), which has been shown to contain vitamin B2–derived activating ligands [3, 19].

Results

Conclusion