Establishment of non-circulating, tissue-resident anti-viral memory T cells in specific niches of the lung (P3198)

Abstract

Abstract Virus-specific memory T cells residing in mucosal sites play an important role in conferring immune protection against recurrent infections. Here we describe the specific retention of memory T cell populations within distinct lung niches following influenza virus (IAV) infection. We used intravenous infusion of fluorescent antibody to differentiate between T cells in the lung interstitium (protected) and those accessible to circulation (labeled). While naïve mice had a negligible frequency of CD4 T cells in the protected niche, after IAV infection 50-70% of total lung CD4 T cells segregated into the protected niche with 30-40% stably maintained within this niche as memory T cells after viral clearance. IAV-specific memory CD4 and CD8 T cells were highly enriched in the protected population compared to circulating T cells. Protected T cells did not recirculate, unlike labeled memory T cells which continuously circulate through lymphoid tissues and are significantly reduced in the lung when lymphoid egress is inhibited. Confocal microscopy showed that effector and memory CD4 T cells in the protected niche were clustered around airways and bronchovascular bundles, while the labeled CD4 T cells were dispersed randomly within the capillaries of the alveoli walls. Our results demonstrate that, following IAV infection, virus-specific memory T cells are retained in spatially distinct lung niches which may be important for protective immunity to respiratory pathogens.