Human ?d T cells in diverse tissues exhibit site-specific maturation dynamics across the life span

Early in ontogeny, gd T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity, though their function in human tissues is not clear. Through analysis of gd T cells in mucosal and lymphoid tissues across the human lifespan, we reveal age- and site-specific differentiation states, functions, and dynamics. Pediatric tissues uniquely contain newly generated gd T cells with diverse repertoires, exhibiting tissue repair and effector functions. In adult tissues, gd T cells persist in lower frequencies, exhibiting highly expanded repertoires and cytolytic profiles. Over childhood, gd T cells convert to adult-like differentiation profiles in mucosal sites, revealing that gd T cells provide diverse recognition and functions for numerous antigenic challenges during early life but persist as terminally differentiated, innate-like cells thereafter. Overall design: gd T cells were isolated by Fluorescence-activated cell sorting from five tissue sites (spleen, lung, LLN, jejunum, MLN) of four human organ donors between the ages of 1.3 and 2 years of age. Individual samples i.e. single organs from each donor, were stained with a unique CITE-seq hashtag and analyzed using scRNAseq