Sensing and alarm function of vaccine-elicited SIV-gag specific CD8 TRM in the reproductive mucosa of rhesus macaques

Abstract Resident memory T cells (TRM) constitute a recently identified lymphocyte lineage that occupies non-lymphoid tissues (NLT) without recirculating. In murine models, upon antigenic rechallenge, TRM trigger antiviral responses in neighboring innate and adaptive immune cells, recruit effectors from circulation. Collectively this is referred to as ‘sensing alarm’ function. However, the full range of functions has not been assessed, non-human primate/human function remains almost entirely uncharacterized. Here we established prime-boost vaccine modality rhesus macaques generate abundant SIV-gag-specific CD8 female reproductive tract (FRT) 14 other NLTs. Upon vaginal challenge with CM9 peptide SIV gag protein, reactivation induced expression CD69 granzyme B SIV-gag specific throughout FRT, situ proliferation (Ki67 expression), rapid IFN response gene essentially all hematopoietic non-hematopoietic cells. Upregulation effector genes CD4 NK ILCs peaked at 24h persisted 48h. CITE-Seq analysis revealed mucosal expressed including HIV restriction factors had reduced HIV-co-receptor CCR5. Increased numbers plasma coincided increased chemokines VCAM-1 on endothelial stromal concomitant reduction circulating These data demonstrate local activation mobilization innate, cellular, humoral site antigen exposure primates.