IL‐21 Selectively Augments Cytotoxic Potential of Antigen‐Activated MAIT Cells

Mucosal‐associated invariant T (MAIT) cells are unconventional cytotoxic T cells restricted by MHC class 1 related molecule, MR1. They are activated through their T cell receptor (TCR) by derivatives from microbial riboflavin synthesis or independently of TCR signalling via IL‐12 and IL‐18. Upon activation, MAIT cells upregulate cytotoxic molecules granzyme B and perforin and lyse bacterially‐infected cells. While cytokines act as co‐stimulatory molecules that enhance MAIT cell activation, their specific role in regulating MAIT cell cytotoxicity remains unresolved. We show that the cytokine IL‐21 enhances expression of granzyme B and perforin on TCR or IL‐12/IL‐18‐activated MAIT cells but has a limited effect on MAIT cell cytokine production. Using a flow cytometry‐based cytotoxic assay, we show priming MAIT cells with IL‐21 enhances their ability to kill 5‐OP‐RU‐treated B cell lines. We demonstrate a previously unexplored co‐stimulatory role for IL‐21 that selectively augments the cytotoxic potential of MAIT cells.