To investigate the reduced efficacy of vaccines in older people due to immune aging, we conducted a comprehensive analysis of the CD4+ T cells, which are important for proper antibody induction.
These findings highlight the positive effects of regular physical activity on frailty, vaccine response, and immunosenescence. They also provide insights into immune changes with aging that affect vaccine efficacy, supporting the development of strategies to improve CD4+ T cell functionality and enhance vaccine effectiveness in older adults.
We found that vaccine-induced CD4+ T cells specific for influenza or Pneumococcal antigens present in the vaccines were less capable of secreting multiple cytokines simultaneously in older subjects, indicating functional defects of these cells.
We observed that a specific subset of CD4+ T cells, so called follicular helper cells (Tfh), which interact with B cells in the tissues to induce antibody production, were reduced in older subjects compared to younger subjects.
Influenza-specific antibodies correlated with these circulating Tfh cell frequencies in the older donor group, indeed highlighting the importance of these cells in generating good vaccine antibody responses. However, CD4+ T cells did not show increased senescence markers, unlike CD8+ T cells and B cells. This suggests that the functional alterations observed in vaccine-specific CD4+ T cells are not due to or associated with overall increased senescence of this compartment.
We also studied metabolic processes, important for converting nutrients into energy for cellular processes for differentiation and proliferation, in the naive T cells. We identified specific metabolic profiles in naive T cells that correlated with better vaccine responses. Specifically, we observed enhanced expression of nutrient receptors in naive CD4+ T cells from vaccine responders compared to non-responders. Moreover, T cells from vaccine responders were characterized by more active metabolism and, more importantly, engaged in a more potent metabolic switch upon activation
Finally, we explored the impact of physical activity (PA) on frailty, vaccine response, and immunosenescence. Subjects aged ≤65 years who engaged in PA for 5-7 days/week had a lower frailty index compared to those who engaged in less PA, although their overall vaccine response was similar. In contrast, older donors who engaged in PA for 5-7 days were more likely to develop strong immune responses towards different/multiple? vaccines. The effect of PA was also measured in a parallel cohort, where we observed that subjects who engaged in PA experienced a significant increase over time in both naive CD4+ and CD8+ T cells.
