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

Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that aid in protection against bacterial pathogens at mucosal surfaces via release of inflammatory cytokines and cytotoxic molecules. Recent evidence suggests MAIT cells are capable of providing B cell help. In this study, we describe a previously unreported population of CXCR5 + T follicular helper (Tfh)-like MAIT cells, MAITfh, that have the capacity to provide B cell help within mucosal lymphoid organs. MAITfh cells are preferentially located near germinal centers in human tonsils and express the classical Tfh-associated transcription factor, B-cell lymphoma 6 (BCL-6), co-stimulatory markers, inducible T cell costimulatory (ICOS) and programmed death receptor 1 (PD-1), and cytokines, interleukin (IL)-21. Furthermore, we demonstrate the ability of MAIT cells to provide B cell help in vivo following mucosal challenge with Vibrio cholerae . Specifically, we show that adoptive transfer of MAIT cells into αβ T cell-deficient mice promoted B cell differentiation and increased serum V. cholerae -specific IgA responses. Our data demonstrate the capacity of MAIT cells to participate in adaptive immune responses, and suggest that MAIT cells may be potential targets for mucosal vaccines. One Sentence Summary We identified and characterized a novel subset of T follicular helper-like MAIT (MAITfh) cells that has the capacity to provide B cell help, and show the sufficiency of MAIT cells to promote production of pathogen-specific IgA antibodies and B cell differentiation in mucosal challenge.