Endurance Exercise Found to Influence PD-1 Expression by CD8+ T Cells

A woman jogging in the early morning.
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Researchers from TU Dortmund in Dortmund, Germany, and the German Sports University in Cologne, Germany, have found that bouts of acute exercise influence the expression level of programmed cell death protein 1 (PD-1), a molecule important to the activity of CD8+ T cells and other subsets of white blood cells in various chronic diseases including cancer.

Their results, published in the European Journal of Applied Physiology under the title “Acute exercise impacts AhR and PD-1 levels of CD8+ T-cells—Exploratory results from a randomized cross-over trial comparing endurance versus resistance exercise”, provide novel insight into mechanisms by which exercise influences the immune system and have implications for the understanding of the association between exercise and human health.

The team of scientists, led by Dr. Philipp Zimmer from the Institute for Sport and Sport Science at TU Dortmund, explored a critical link between exercise and the activity of the immune system, the aryl hydrocarbon receptor, which is an intracellular protein that translocates from the cytoplasm to the nucleus of cells upon activation, promoting changes in the expression of various genes including that encoding programmed cell death protein 1 (PD-1).

Since exercise influences the levels of kynurenine (KYN), a molecule that activates the aryl hydrocarbon receptor, the team thus sought to determine whether exercise could, correspondingly, be associated with changes in the expression level of PD-1, which is present on the surface of some white blood cell populations and can regulate their responsiveness to tumors and activity in other contexts such as autoimmune disease.

Based upon this link between exercise and the activity of the immune system, the team hypothesized that “endurance exercise results in a greater decrease in the cytoplasmatic AhR level, whereas surface PD-1 levels show a greater increase.”

“Since the impact of acute exercise on the KYN pathway towards [its metabolite kynurenic acid] KA has been described to be more pronounced following endurance than resistance exercise, and both KYN and KA are endogenous ligands of the AhR, we expect greater changes induced by endurance exercise,” the authors stated in their publication.

The scientists tested their hypothesis by assessing the quantity and characteristics of T cells isolated from blood samples of 24 healthy males (age: 24.6 ± 3.9 years; weight 83.9 ± 10.5 kg; height: 182.4 ± 6.2 cm) that completed a “single bout of endurance (EE) and resistance exercise (RE) in a randomly assigned order on separate days.”

Populations of T cells were found to change over time, “indicated by an increase in the absolute numbers of CD3+ lymphocytes after EE (p < .001) and RE (p = .036) and in PD-1+ CD8+ T-cells after EE (p = .021).”

“Proportions of T-cell populations changed only after EE (t0–t2: p = .029; t1-t2: p = .006). The level of cytoplasmic AhR decreased immediately after exercise in both exercise conditions (EE: p = .009; RE: p = .036). The level of surface PD-1 decreased 1 h after EE (p = .005).”

The scientists concluded that endurance exercise in particular “was observed to impact both AhR and PD-1 levels, undermining its role as the AhR-PD-1 axis modulator.”

The team’s data could help to explain known associations between physical activity, which “has been shown to reduce cancer incidence and inhibit tumor growth“, and human health. Exercise was previously shown to reduce the incidence and progression of tumors in a mouse model of breast cancer. Further research into mechanisms underlying the link between exercise and cancer prevention in humans is warranted.

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Schenk, A., Joisten, N., Walzik, D. et al. Acute exercise impacts AhR and PD-1 levels of CD8+ T-cells—Exploratory results from a randomized cross-over trial comparing endurance versus resistance exercise. Eur J Appl Physiol (2020).