Defining resident memory T cell differentiation and function in non-human primates 4479

Abstract

Abstract Description Antigen-experienced lymphocytes can be equilibrating (continuously migratory between blood and peripheral tissues) or resident (stably surveilling within tissues). Because migration is difficult to measure outside of mice, it is common to extrapolate phenotypic proxies of residence derived from mouse studies to other species. We wished to more rigorously assess the differentiation state and function of equilibrating vs. resident memory CD8+ T cells (TRM) in nonhuman primates (NHP). To this end, we delivered a heterologous prime-boost-boost (HPBB) vaccine to both mice and Indian rhesus macaques that resulted in preternaturally abundant memory CD8 T cells that were distributed in over 30 anatomical sites. We then conducted a constellation of assays to infer migration properties of primate T cells: through single cell genomic analyses of paired mouse vaccinees that underwent parabiotic migration tests, through staged intravascular staining in NHP, and through comparisons of systemic and local routes of immunization. These data informed a cross-species signature that correlated with T cell migration properties. Functional assays were performed in NHP by reactivating memory CD8 T cells in situ and ex vivo, revealing that Trm are uniquely poised to communicate reactivation events to neighboring immune and stromal cells. Funding Sources Bill and Melinda Gates Foundation (OPP1116224, D.M.) NIH grants AI090732 and 5R01AI084913-14 (D.M.) U19AI096187, UM1AI124436 and UM1AI169662 (E.H and R.R.A) NCRR/NIH base grant P51 OD011132 to Emory National Primate Research Center. Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)