Mucosal-Associated Invariant T Cells in Tuberculosis Pleurisy

Abstract

Mucosal-Associated Invariant T (MAIT) cells, which is a prevalent and unique innate T-cell population that expresses an evolutionarily conserved invariant T cell receptor TCRVα7.2, are present at high frequencies at mucosal tissue sites and have an intrinsic capacity to respond to microbial infections. However, the local immune responses of MAIT cells at the site of M.tb infection is unclear. We compared the PFMCs from TB (n = 57) with the PBMCs from TB (n = 57) and HD (n = 50), and characterized those T-cell phenotypes and functions. Our direct ex vivo analysis demonstrated that the frequencies of MAIT cells in PFMCs were much higher than those in PBMCs from TBP patients (P<0.001), however, lower than those in PBMCs from HD (P<0.01). Those infiltrating MAIT cells expressed high levels of tissue-tropism chemokine receptors (CXCR3hiCXCR4hiCXCR6hiCCR6hiCXCR5hiCCR5hi) and displayed an effector memory phenotype (CD45RO+CCR7-CD62L-), which indicated preferential accumulating these cells into infected lung lesions. Further, the majority of MAIT cells in PFMCs expressed CD69, a marker for tissue resident memory T cells, which suggested that specialization of these T cells into unique tissue-resident subsets given the host enhanced regional immunity. In addition, MAIT cells from PFMCs produced IFN-γ and TNF-α, and exhibited cytotoxic activity molecules CD107a/b, suggesting that poly functional M.tb-reactive MAIT cells played an significant role against M.tb infection in the local lesions. This study addressed that the M.tb-reactive MAIT cells exerted unique innate functions in immune responses to M.tb at local infection sites.