Age-associated change in the frequency of memory CD4⁺ T cells impairs long term CD4⁺ T cell responses to influenza vaccine

We investigated the relationship of memory CD4⁺ T cells with the evolution of influenza virus-specific CD4⁺ T cell responses in healthy young and elderly people. Elderly individuals had a similar frequency of CD69⁺CD4⁺ T cells producing IFN-γ and TNF-α at 1 wk, but a lower frequency of these CD4⁺ T cells at 3 mo after influenza vaccination. Although the elderly had a higher frequency of central memory (CM; CCR7⁺CD45RA^-) CD4⁺ T cells, they had a significantly lower frequency of effector memory (EM; CCR7 ^-CD45RA^-) CD4⁺ T cells, and the frequency of the latter memory CD4⁺ T cells positively correlated with the frequency of influenza virus-specific CD69⁺CD4⁺ T cells producing IFN-γ at 3 mo. These findings indicate that the elderly have an altered balance of memory CD4⁺ T cells, which potentially affects long term CD4⁺ T cell responses to the influenza vaccine. Compared with the young, the elderly had decreased serum IL-7 levels that positively correlated with the frequency of EM cells, which suggests a relation between IL-7 and decreased EM cells. Thus, although the healthy elderly mount a level of CD4⁺ T cell responses after vaccination comparable to that observed in younger individuals, they fail to maintain or expand these responses. This failure probably stems from the alteration in the frequency of CM and EM CD4⁺ T cells in the elderly that is related to alteration in IL-7 levels. These findings raise an important clinical question about whether the vaccination strategy in the elderly should be modified to improve cellular immune responses.