T helper subset distribution changes with age and is influenced by IL-2 (LYM2P.724)

To better understand how aging impacts the immune response to influenza infection, we have examined CD4+ T helper (Th) subsets and how they are impacted by aging. Th cells are important for helping Ab production by B cells and are required for the generation of cytotoxic and memory CD8⁺ T cells. Influenza nucleoprotein (NP)-specific Th subsets can be distinguished by PSGL1 and Ly6C expression: PSGL1hiLy6Chi cells are terminally differentiated Th1 effectors; PSGL1hiLy6Clo cells are more memory-like; PSGL1loLy6Clo cells are mostly T follicular helper (Tfh)-like. With age, the proportion of PSGL1hiLy6Chi Th1 effectors is reduced and Tfh-like PSGL1loLy6Clo cells are increased both in naïve mice and during infection. Additionally, Tfh cells (defined as CXCR5+PD-1+) are also increased with age. This change in subset distribution with age is also associated with a decrease in ex vivo IL-2 levels in aged animals. In order to further examine how IL-2 can impact subset distribution, an in vitro system was used in which CD4 T cells from young, middle aged and aged mice were cultured with anti-CD3/anti-CD28. Addition of exogenous IL-2 to Th cells from all age groups resulted in reduction of the PSGL1loLy6Clo Tfh population. Furthermore, blocking IL-2 with anti-CD25 Ab increased the PSGL1loLy6Clo Tfh population, regardless of age. Thus, the availability of IL-2, independent of aging, influences Th subset distribution and can account for the increase in Tfh with aging.