Pro-inflammatory adjuvants enhance the cognate helper activity of aged CD4 T cells (96.9)

Abstract The humoral response in aged individuals is significantly reduced compared to young, thus contributing to the reduced efficacy of vaccines commonly seen in older populations. Using an adoptive transfer model, we have shown that age-related intrinsic declines in the function of naïve CD4 T cells from aged donors contribute significantly to reduced humoral responses. This decline leads to reduced B cell expansion and differentiation as well as reduced IgG production. In this study, we show that the helper function of aged CD4 T cells can be enhanced using a Toll-like receptor (TLR) binding adjuvant or an adjuvant containing proinflammatory (PI) cytokines. In addition, we show that the helper function of aged CD4 T cells can be enhanced by adding PI cytokines during in vitro effector generation. We observed enhanced expansion and differentiation of B cells and affinity maturation of IgG. Importantly, we found that PI cytokines also induced significant production of a variety of effector cytokines, including IL-4, IFNg, IL-17, and IL-21, by both young and aged CD4 T cells. The use of PI adjuvants can also improve humoral responses in intact aged animals. We propose that one of the mechanisms involved in the ability of adjuvants to enhance both young and aged T cell responses includes driving multifaceted T cell differentiation and production of multiple cytokines by responding T cells. This work funded by NIH grants AG21054 and AG02160 to LH.