A novel subset of follicular helper-like MAIT cells has capacity for B cell help and antibody production in the mucosa.

Abstract

Abstract Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that respond to conserved microbial metabolites presented on the evolutionarily conserved MHC class I-related protein, MR1. MAIT cells are enriched in the mucosa and aid in protection against bacterial pathogens via release of inflammatory cytokines and cytotoxic molecules. Recent evidence suggests MAIT cells are capable of providing B cell help in vitro and in vivo. In this study, we used primary human samples and mouse models to uncover the role of MAIT cells in B cell help at the mucosa. Here we describe a novel population of CXCR5+ T follicular helper (Tfh)-like MAIT cells (MAITfh) that are enriched in human mucosal lymphoid tissues. Using in vitro culture assays and fluorescence imaging, we found that MAITfh cells preferentially locate within germinal centers in human tonsils and express the canonical Tfh transcription factor, B-cell lymphoma 6 (BCL-6), co-stimulatory markers, inducible T cell costimulator (ICOS), and programmed death receptor 1 (PD-1), and cytokines, interleukin (IL)-21, IL-10, and BAFF. Furthermore, we investigate the sufficiency of MAIT cells to aid in antibody mediated immunity in vivo using a mouse model of MAIT adoptive transfer followed by mucosal challenge with live Vibrio cholerae. We show that adoptive transfer of MAIT cells into αβ T cell deficient mice promotes B cell differentiation and increased serum V. cholerae-specific IgA and bactericidal responses. Our data demonstrate the capacity of MAIT cells to participate in adaptive immune responses at the mucosa, and suggest MAIT cells may be potential targets to improve mucosal vaccines.