MAIT cell-mediated cytotoxicity: Roles in host defense and therapeutic potentials in infectious diseases and cancer

Mucosa-associated invariant T (MAIT) cells are unconventional, innate-like T lymphocytes that sense the presence of MHC-related protein 1 (MR1)-restricted ligands and select inflammatory cues. Consequently, they release potent immunomodulatory mediators, including IFN-gamma, TNF-alpha, and/or IL-17. MAIT cells can also be viewed as killer cells. They display several NK cell-associated receptors, carry granules containing cytotoxic effector molecules, and swiftly upregulate perforin and granzymes upon activation. Accordingly, MAIT cells are capable of lysing MR1-expressing cells infected with a variety of pathogenic bacteria in in vitro settings and may also mount cytotoxic responses during microbial infections in vivo. Of note, MAIT cell hyperactivation during certain infections may impede their ability to elicit inflammatory and/or cytotoxic responses to secondary stimuli. In addition, MAIT cells isolated from within and from the margin of tumor masses exhibit diminished functions. We propose that MAIT cell-mediated cytotoxicity can be induced, bolstered, or restored to assist in clearing infections and potentially in reducing tumor loads. In this review, we discuss our current understanding of MAIT cells' lytic functions and highlight the pressing questions that need to be addressed in future investigations. We also offer a picture, however hypothetical at this point, of how harnessing the full cytotoxic potentials of MAIT cells may be a valuable approach in the immunotherapy of infectious and malignant diseases.