Impact of aging on CD4 T cell helper functions

Impairment of the immune system in older people leads to increased susceptibility to infection and reduced antibody production following immunization. We have previously shown that intrinsic defects in CD4 T cell function occur in aged mice and that this negatively impacts the antibody response. In addition, other age-related changes can impact CD4 T cell priming. Using an adoptive transfer model, we show that the trafficking of young TCR Tg CD4 T cells to the T cell zones of secondary lymphoid organs is impaired when they are transferred into aged hosts compared to young hosts. This correlates with delayed expansion and reduced activation as measured by CFSE dilution and CD69 expression, respectively. Using immunofluorescent staining of spleen sections, we demonstrate that the structure of the B cell follicles and the expression of CCL21 are disorganized in aged hosts compared to young hosts, likely causing this reduced trafficking in aged hosts. This also likely contributes to the reduced induction of Tfh cells in the lymph nodes of aged mice. Finally, we found that fewer aged cells produce cytokines and that the pattern of cytokine production is also different, aged mice having more cells producing IL-17 but less cells producing IL-4, IL-10 and IFNγ than young mice. Thus, not only is the CD4 T cell response reduced with age, it is also qualitatively different which could account for reduced induction of protection following immunization.