Primate resident memory T cells activate humoral and stromal immunity [Bulk RNA-seq]

CD8 resident memory T cells (Trm) comprise a small population of frontline sentinels compared to the large tissues they surveil. CD8 Trm make outsized contributions to immune protection from infection, yet underlying mechanisms are not well understood. This study interrogated mechanisms of Trm function in primates. We show that intravenous immunization of macaques with an SIV-gag-containing heterologous prime-boost-boost vaccine establishes memory T cells in >30 tissues, including visceral and mucosal compartments. We next developed methods for reproductive tract CD8 Trm reactivation in vivo. Upon antigen-sensing, CD8 Trm activated local stromal, parenchymal, and innate and adaptive immune cells. Stromal and parenchymal cells accentuated leukocyte homing and antiviral defenses. B and plasma cells were mobilized in the vaginal mucosa and bloodborne CD4 T cells were recruited and adopted an infection-resistant phenotype. In conclusion, Trm repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals and activate diverse host defenses. Overall design: Female Indian Rhesus macaques were SIV-gag vaccinated. Animals were challenged intravaginally with CM9 peptide for 24 or 48h or left unchallenged. Bulk RNA sequencing was performed on all cells from the vagina, ectocervix, endocervix, or uterus or from a combination of cervical and vaginal CM9-specific CD8 T cells.