In vivo labeling reveals that degranulation is increased under supraphysiological TCR stimulation, but not microbial exposure, in effector memory T cells from old mice 3691

Abstract Description CD8+ T cells exhibit distinct changes with age, including a diminished naïve cell pool, expansion of memory and exhausted cells, and altered effector function, increasing susceptibility to infection. They also show reduced cytotoxicity in vivo but increased granule content and faster cytotoxic kinetics in vitro. Whether CD8+ T cells from old mice degranulate when activated in vivo within the aged environment is unknown. We investigated the in vitro and in vivo degranulation of CD8+ T cells from young and old mice during supraphysiological aCD3 stimulation and petstore cohousing challenge. Actively degranulating CD8+ CD44+ T cells were identified by labeling during a two-hour incubation with granule-specific antibodies (CD107a/CD107b). Our findings reveal that CD8+ T cells from old mice challenged with supraphysiological TCR stimulation exhibited higher degranulation than young mice. This effect is more prominent in vitro and can be explained by the increase in effector memory, compared to central memory cells with age. However, during microbial exposure, CD8+ T cells from old mice fail to degranulate, consistent with the reduced cytotoxic capacity. These data highlight the preserved cytotoxic capacity of memory CD8+ T cells from old mice and suggest that the aged microenvironment and stimulation type contribute to lower degranulation and cytotoxic capacity. This provides insight into the potential of increasing T cell activation to improve vaccine approaches in the elderly. Funding Sources Supported by NIH R00AG058800, NIH R21AG078638, NIH R01AG079913-01, NIH T32AG029796, the Fesler-Lampert Chair in Aging Studies, the Glenn Foundation for Medical Research/AFAR Grants for Junior Faculty, and The McKnight Land-Grant. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)