Age-Associated Change in the Frequency of Memory CD4+ T Cells Impairs Long Term CD4+ T Cell Responses to Influenza Vaccine

Abstract

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.

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

“…These results are in agreement with those of Aggarwal and Gupta, who showed that increased caspase-3 expression and decreased Bcl-2 expression in CD45RA + and CD45RO + T cells of aging humans mediated an increased susceptibility to apoptosis Gupta 1998, 1999). A possible explanation for the age-associated proneness to spontaneous apoptosis is the decreases in both IL-7 levels and IL-7 receptor with aging (Kim et al 2006;Kang et al 2004). The IL-7 pathway is necessary for the development and survival of memory T cells by upregulating Bcl-2 pro-survival proteins (Chetoui et al 2010).…”

The effect of aging on cognate function and development of immune memory

“…Another recent study examined the generation of CD4 + memory T cells following influenza vaccination of young and aged adults [20]. This study found that the frequency of virusspecific CD4 + T cells from the peripheral blood that secreted IFN-γ or TNF-α upon ex vivo re-stimulation was significantly reduced in the elderly subjects three months postimmunization.…”

Immunogenicity of influenza A(H1N1)pdm09 vaccine in patients with diabetes mellitus

“…We found that the following [10][11][12] and seasonal influenza vaccine. [13][14][15] Compromised nutritional status [16][17][18] and decreased T-cell activity [18][19][20] could be contributing factors for that finding. One study in patients with hepatitis C reported a decreasing effect of lower BMI on immune response to A(H1N1)pdm09 vaccine.…”