Cervicovaginal Tissue Residence Confers a Distinct Differentiation Program upon Memory CD8 T Cells

Tissue-resident memory CD8 T cells (CD8 T_RM) are critical for maintaining barrier immunity. CD8 T_RM have been mainly studied in the skin, lung and gut, with recent studies suggesting that the signals that control tissue residence and phenotype are highly tissue dependent. We examined the T cell compartment in healthy human cervicovaginal tissue (CVT) and found that most CD8 T cells were granzyme B⁺ and TCF-1^- To address if this phenotype is driven by CVT tissue residence, we used a mouse model to control for environmental factors. Using localized and systemic infection models, we found that CD8 T_RM in the mouse CVT gradually acquired a granzyme B⁺, TCF-1^- phenotype as seen in human CVT. In contrast to CD8 T_RM in the gut, these CD8 T_RM were not stably maintained regardless of the initial infection route, which led to reductions in local immunity. Our data show that residence in the CVT is sufficient to progressively shape the size and function of its CD8 T_RM compartment.