Defining the role of mucosal-associated invariant T (MAIT) cells in B cell help

Abstract

Abstract Pathogen-associated diarrheal diseases account for over 1.6 million deaths annually, yet the number of effective mucosal vaccines remains limited. An exciting potential target for mucosal vaccine adjuvants are mucosal-associated invariant T (MAIT) cells. MAITs are innate-like T cells which are found in the mucosa, blood, and secondary lymphoid organs (SLO), and can respond rapidly to conserved microbial antigens through cytokine secretion and cytotoxic effects. Recent evidence supports a role for MAITs in B cell help. We aim to improve mucosal vaccines by investigating a novel subset of T follicular helper (Tfh)-like MAIT cells and their ability to aid in B cell help and antibody mediated immunity. We describe Tfh-like MAITs from human blood and tonsil samples using linked TCR and phenotype single cell RNAseq, and in vitro culture assays. We further investigate the sufficiency of MAITs aid in antibody mediated immunity in vivo using a MAIT adoptive transfer model into Tcratm1Mom/J (αβ T cell deficient) mice followed by mucosal bacterial challenge. We identify a subset of CXCR5+ MAITs, enriched in human tonsils and murine SLOs that express the Tfh lineage defining transcription factor, BCL6, co-stimulatory markers and cytokines including IL-10 and IL-21 and can aid in B cell help in vitro. Likewise, in vivo we find that MAIT transfer induces pathogen-specific IgA but not IgG responses following mucosal challenge. Overall our study uncovered a novel subset of Tfh-like MAITs and has demonstrated the capacity of MAITs to provide help in antibody responses. Current work aims to uncover the mechanism of MAIT-B cell help which could critically inform efforts to target this population as mucosal adjuvants.