Concomitant assessment of PD-1 and CD56 expression identifies subsets of resting cord blood V82 T cells with disparate cytotoxic potential

Vy9V82 T lymphocytes are programmed for broad antimicrobial responses with rapid production of Th1 cytokines even before birth, and thus thought to play key roles against pathogens in infants. The process regulating V82 cell acquisition of cytotoxic potential shortly after birth remains understudied. We observed that perforin production in cord blood V82 cells correlates with phenotypes defined by the concomitant assessment of PD-1 and CD56. Bulk RNA sequencing of sorted V82 cell fractions indicated that transcripts related to cytotoxic activity and NK function are enriched in the subset with the highest proportion of perforin+ cells. Among differentially expressed transcripts, IRF8, previously linked to CD8 T cell effector differentiation and NK maturation, has the potential to mediate V82 cell differentiation towards cytotoxic effectors. Our current and past results support the hypothesis that distinct mechanisms regulate V82 cell cytotoxic function before and after birth, possibly linked to different levels of microbial exposure.