Exploring the functionality of CD56+ MAIT cell populations across human tissues

Abstract

Abstract Mucosa-associated invariant T (MAIT) cells are an evolutionarily conserved population of T cells serving a sentinel function at mucosal barrier sites to mediate immune protection. MAIT cells utilize their semi-invariant T cell receptor (TCR) to react to non-peptidic antigens derived from microbial riboflavin metabolites, presented on monomorphic MHC-class I-like MR1 molecules. In addition to TCR-dependent recognition of vitamin B2metabolites, MAIT cells sense and respond to local inflammatory cytokines in an innate-like manner. Surface expression of CD56 was previously shown to be associated with enhanced MAIT cell sensitivity to TCR-independent activation. However, the regulation, frequency, or relevance of CD56 expression on human MAIT cells is currently not well understood. Flow cytometry revealed heterogeneity of CD56 expression across donor-matched tissues obtained from human organ donors. Strikingly, the majority of liver MAIT cells expressed CD56, whereas expression was consistently lower in other tissues. We evaluated de novo CD56 expression on blood-derived sorted CD56-negative MAIT cells following IL-7 or antigen exposure which is likely to occur in the hepatic acute phase response. CD56-negative MAIT cells strongly upregulated CD56 expression after IL-7 stimulation and maintained CD56 expression for up to 19 days. Exposure to MR1-presented antigen induced CD56 expression similarly but required prior cell proliferation. In summary, we identify heterogeneity between MAIT cell populations of different tissue origin and determine the dynamic regulation of the CD56-associated innate-like characteristics to shed light on unknown aspects of MAIT cell diversity and immunobiology.