• Innate specific lysis activity is lower in cisgender women than cisgender men • Individual patterns of innate cytotoxic potential are influenced by sex hormones • Gender affirming hormone therapy could affect innate specific lysis in transgender individuals • Immune cells isolated from the rectal mucosa are able to potently mediate cytotoxicity Sex hormones contribute to sexually dimorphic immunological outcomes, including the innate cytotoxic capacity of Natural Killer (NK) cells in populations of cisgender individuals, but has yet to be evaluated in transgender individuals. Here, we quantified innate cytotoxic capacity of circulating PBMC using a K-562-GFP killing assay within a sex and gender inclusive cohort. We observed PBMC specific lysis activity was significantly lower in cisgender women as compared to cisgender men, with specific lysis values of transgender women and men falling within this range. Serum estradiol was negatively associated with PBMC specific lysis, while testosterone and the percentage of CD56+CD16+ NK positively associated with PBMC specific lysis. Exploratory assays with rectal mucosal cells demonstrated robust innate cytotoxic potential, which did not correlate with systemic measures in this subset of study participants. These data suggest innate cytotoxic functions are influenced by individuals’ unique sex hormonal profiles, and could differ by tissue compartment of interest.
Jung et al. (Wed,) studied this question.
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