MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8+ MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissue-repair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8+ MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.
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MAIT cells, TCR signaling, cytokines, effector functions, tissue repair, Aged, Aged, 80 and over, CD8-Positive T-Lymphocytes, Caco-2 Cells, Cytokines, Female, Humans, Inflammation, Lymphocyte Activation, Male, Middle Aged, Mucosal-Associated Invariant T Cells, Receptors, Antigen, T-Cell, Signal Transduction, THP-1 Cells