Seminar Title: Primate resident memory CD8 T cells activate humoral and stromal immunity

Seminar Abstract: Resident memory CD8 T cells (Trm) mediate tactile tissue immune surveillance that requires cell-to-cell contact for pathogen/antigen recognition. Despite comprising a small minority of cells within barrier sites, Trm appear to make outsized contributions to protection from reinfection, yet underlying mechanisms are not well understood, especially in humans and non-human primates (NHP). This study interrogated mechanisms of Trm function in primates. Macaques were iteratively vaccinated i.v. with an SIV-gag containing heterologous prime boost vaccine that established memory T cells in over 30 tissues including visceral and mucosal compartments. We next developed methods for CD8 Trm reactivation in vivo in female reproductive mucosae. Cognate antigen-sensing was limited to gag-specific CD8 Trm, which activated local stromal, parenchymal, and immune cells. Trm activated tissue fibroblasts which amplified leukocyte homing and antiviral defenses. CD8 Trm reactivation also activated humoral immunity in the vaginal mucosa, recruited bloodborne CD4 T cells, and imprinted the latter with an S/HIV-resistant phenotype. Overall, this study reports that upon reactivation, CD8 Trm repurpose their more abundant neighbors - stromal, parenchymal, and innate and adaptive immune cells to augment alarm and activate diverse host defenses.