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IL-6 production by TLR-activated APC broadly enhances aged cognate CD4 helper and B cell antibody responses in vivo #MMPMID28250157
J Immunol 2017[Apr]; 198 (7): 2819-33 PMID28250157show ga
Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pre-treated ex vivo with TLR agonists, polyI:C and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG antibody production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond sub-optimally to IL-6 compared to the young, such that higher doses are required to induce comparable signaling. Pre-activating APC overcomes this deficiency. Responses of young CD4 T cells are also enhanced by pre-activating APC with similar effects but with only partial IL-6 dependency. Strikingly, introducing just the activated APC into aged mice significantly enhances otherwise compromised antibody production to inactivated influenza vaccine. These findings reveal a central role for production of IL-6 by APC during initial cognate interactions in the generation of effective CD4 T cell help, which becomes greater with age. Without APC activation aging CD4 T cell responses shift towards IL-6-independent Th1 and ThCTL responses. Thus, strategies that specifically activate and provide antigen to APC could potentially enhance Ab mediated protection in vaccine responses.