Acute Aerobic Exercise Preferentially Mobilizes Dominant T-cell Clones To Transiently Lower Receptor Polyclonality In Circulation

Abstract

Exercise mobilizes and redistributes large numbers of memory T-cells, which may contribute to enhanced immune surveillance in regular exercisers. The diversity of T-cell receptors (TCRs) is vital for the human immune system to recognize a host of foreign antigens, but how exercise affects dynamic changes in antigen specific T-cells at the clonal level is not known. PURPOSE: Determine the effect of acute exercise on T-cell clonality and diversity. METHODS: Healthy volunteers (age 21-41 years) completed an incremental continuous cycling bout consisting of 4x5-minute stages at pre-determined power outputs ranging from 50% to 80%, of VO2peak. DNA was extracted from peripheral blood mononuclear cells (PBMCs) collected at rest, during exercise at 80% VO2peak, and 1 hr post, and underwent high throughput TCR-β chain sequencing via Adaptive Biotechnologies. Data was analyzed utilizing the immunoSEQ® Analyzer online software platform. RESULTS: The top ten ranked productive clones were significantly elevated during exercise (p < 0.005) and were mobilized by a greater magnitude compared to compared to less frequent productive clones. As such, the number of unique productive clones was significantly lower at 80%-intensity exercise compared to rest (p = 0.032) and 1 hr-post (p = 0.046). Additionally, TCR clones found during exercise demonstrate a trended decrease in clonal diversity as indicated by Simpson’s D (p = 0.068) and Shannon’s Entropy (p = 0.088). CONCLUSIONS: Exercise mobilizes the most dominant T-cell clones within the repertoire resulting in a less polyclonal repertoire of T-cells in the circulation. This indicates that exercise preferentially mobilizes T-cell clones with specificity to antigens the host has previously encountered. Subsequent work will determine if exercise drives a preferential mobilization of clones that share TCR motifs and clustered networks associated with cytotoxicity, tumor-antigen specificity, and viral experience.