Adjuvants enhance the cognate function of aged CD4 T cells via a mechanism involving IL-17 production

The humoral response in aged humans and mice is significantly reduced compared to young and is a contributing factor in the reduced efficacy of vaccines seen in aged populations. Using an adoptive transfer model comparing young and aged T cell receptor transgenic (TCR Tg) CD4 T cells in young hosts, we have shown that age‐related declines in CD4 T cell function contributed greatly to the reduced humoral responses observed in the aged. This decline leads to reduced B cell expansion and differentiation as well as reduced IgG production. The helper function of aged CD4 T was enhanced using a combination of inflammatory cytokines (TNF alpha, IL‐1 and IL‐6) or adjuvants that induce these cytokines. In addition, the helper function of aged CD4 T cells was also enhanced when the inflammatory cytokines were added during in vitro CD4 effector generation. In both of these cases, the helper activity of aged CD4 T cells was significantly enhanced, leading to better expansion and differentiation of antigen‐specific B cells. Using real time PCR, we found that these cytokines induced significant production of IL‐17 by the aged CD4 T cells in vitro. We have also gone on to show that Th17 effectors generated in vitro from naive aged CD4 T cells exhibit potent helper activity in our adoptive transfer model. We propose that one of the major mechanisms involved in the ability of adjuvants to enhance T cell responses involves induction of IL‐17 production by the responding CD4 T cells. This work was funded by NIH grant AG02160 to LH.