Exercise Delays T Cell Population Aging

Exercise delays the aging of the immune system, particularly changes in the distribution of T cell populations, but what are the underlying mechanisms? Researchers here note the existing focus in the scientific community on mitochondrial metabolism in T cells; exercise beneficially affects mitochondrial function, and energy metabolism is an important determinant of T cell behavior. The researchers suggest, however, that the existing evidence is more supportive of effects based on differences in metabolite production and consumption. It is an interesting viewpoint.

The effect of exercise on immune health has been widely studied in various population cohorts, however, exercise-research targeting CD4+ T cells is less represented. Nevertheless, exercise has been shown to modulate both the number and activity of CD4+ T cells, with an increased number of CD4+ T cells observed in the blood of athletes after training. Furthermore, physical fitness can modulate the concentration of immune cell subsets (VO2max exhibiting a large correlation with regulatory T cells (Treg) populations in the blood outside of training). Moreover, exercise can alter the balance of Th17/Tregs (increased Th17 and decreased Treg populations) improving chronic heart failure outcomes in a murine model. In reports that have identified CD4+ T cell subsets, the mechanisms driving these observations are not characterized, however, it is likely that metabolism plays an integral part.

Metabolic programs engaged by T cells directly affect their identity and function. Substrate utilization during exercise will vary depending on the exercise type, intensity, and duration. During low to moderate intensity exercise, the main substrates are glucose, glutamine, and fatty acids; with glucose becoming a more prominent fuel source as intensity increases. Considering the importance of mitochondria in cell metabolism, the effects of exercise in mitochondria have been studied extensively. Although it is expected that exercise-related adaptations mainly affect muscle mitochondria, exercise can influence surrounding cells via the availability of metabolites.

In summary, CD4+ T cells include a diverse population with highly varied function. Plasticity is exhibited between CD4+ T cell subsets and linked to numerous maladies such as development and exacerbation of autoimmune disorders and tumorigenesis. Exercise has been shown to effect CD4+ T cells, however, our understanding of the mechanisms surrounding these changes is limited. We propose that exercise could alter CD4+ T cell identity through metabolic responses to exercise, which in turn, affect the availability of metabolites and induce epigenetic remodeling events. To substantiate these claims, more research is needed to profile the epigenetic landscape of CD4+ T cells in response to exercise at the single cell level, identifying intermediate cell subsets, and deciphering the role of exercise on immune cell plasticity.

Link: https://doi.org/10.3389/fimmu.2021.729366

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