A disconnect between precursor frequency, expansion potential, and site-specific CD4⁺ T cell responses in aged mice

T cell recognition of peptides presented within self-major histocompatibility complex (pMHC) molecules is essential for long-lived protective immunity. As mice age the number of naïve CD4⁺ and CD8⁺ T cells declines. However, unlike for CD8⁺ T cells, there are more naïve and memory phenotype CD4⁺ T cells that bind foreign pMHCII in old mice (18–22 months) than adults (12–15 weeks), suggesting increased promiscuity of pMHCII recognition with aging. Here we asked if CD4⁺ T cell responses to immunization or infection increase with aging since the magnitude of a CD4⁺ T cell response to a foreign pMHCII is proportional to the size of the precursor population in adult mice. We observed no difference in the number of pMHCII-specific CD4⁺ T cells in adult versus old mice for pooled secondary lymphoid organs after immunization, bacterial infection, or viral infection, but we did observe diminished numbers of pMHCII-specific CD4⁺ T cells in both the draining lymph node and brain of old mice after West Nile virus infection. These data indicate that an increased precursor frequency does not translate into more robust responses upon immunization or infection in old mice.