Abstract
Abstract An aAge-related decline in cytolytic activity has been mainly described in CD8+ T cells and , with relative sparing of CD4+ T cells. wWe have shown that the poor CD8+ effector T cell response to influenza A/H3N2 challenge is due to a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Hee we report In this study, we showed that therethis response corresponds to a significant decline in IL-2 levels but increased IL-6 levels in influenza-stimulated PBMCs from vaccinated older compared to young adults. We find that addition of exogenous Supplementation of PBMC with IL-2 and IL-6 to PBMC cultures with restoresd the proliferative response and reducesd the proportion of apoptotic effector CD8+ T cells in older adult PBMC to resemble that of younger adults. To further elucidate the mechanism, Wwe finshowed that exogenous IL-2 and IL-6 resulted in the differentiation of naïve CD4+ T cells into effector T helper cells which express IL-2 in response to influenza virus stimulation. Further, use of a TLR4 ligand combined with influenza vaccine ,whichto respectively stimulate IL-6 and IL-2 production, resultsed in an enhanced granzyme B response of aged CD8 T cells to a live influenza virus challenge. These results suggest provide a mechanism that could be targeted in the development of influenza vaccines to potentially with enhance theird efficacy in older adults.