Human Mucosal Associated Invariant T Cells Detect Bacterially Infected Cells

TLDR

Control of Mycobacterium tuberculosis infection relies on Th1-type immunity, with CD8+ T cells playing a unique role, and Mtb‑reactive CD8+ T cells are found at high frequencies in both infected and uninfected humans. The study identifies MAIT cells—Vα7.2+ CD8+ T cells restricted by MR1 and activated TAP‑independently—as universally present, more abundant in uninfected individuals, reduced in peripheral blood of active TB patients, enriched in lung tissue, responsive to Mtb‑infected epithelial cells, and capable of detecting other bacterial infections, indicating a broad role in sensing bacterially infected cells.

Abstract

Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtb-uninfected individuals. Interestingly, these Mtb-reactive cells expressed the Vα7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an “innate” T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection.