Clonal Kinetics and Single-Cell Transcriptional Profiles of T Cells Mobilized to Blood by Acute Exercise

• Published in: Medicine and science in sports and exercise Vol. 55; no. 6; p. 991
• Main Authors: Zúñiga, Tiffany M, Baker, Forrest L, Smith, Kyle A, Batatinha, Helena, Lau, Branden, Burgess, Shane C, Gustafson, Michael P, Katsanis, Emmanuel, Simpson, Richard J
• Format: Journal Article
• Language: English
• Published: United States 01.06.2023
• Subjects: Clone Cells - metabolism; Epstein-Barr Virus Infections - metabolism; Exercise; Herpesvirus 4, Human - metabolism; Humans; Leukocytes, Mononuclear - metabolism; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - metabolism; T-Lymphocytes
• ISSN: 1530-0315
• DOI: 10.1249/MSS.0000000000003130

Acute exercise redistributes large numbers of memory T cells, which may contribute to enhanced immune surveillance in regular exercisers. It is not known, however, if acute exercise promotes a broad or oligoclonal T-cell receptor (TCR) repertoire or evokes transcriptomic changes in "exercise-responsive" T-cell clones. Healthy volunteers completed a graded bout of cycling exercise up to 80% V̇O 2max . DNA was extracted from peripheral blood mononuclear cells collected at rest, during exercise (EX), and 1 h after (+1H) exercise, and processed for deep TCR-β chain sequencing and tandem single-cell RNA sequencing. The number of unique clones and unique rearrangements was decreased at EX compared with rest ( P < 0.01) and +1H ( P < 0.01). Productive clonality was increased compared with rest ( P < 0.05) and +1H ( P < 0.05), whereas Shannon's Index was decreased compared with rest ( P < 0.05) and +1H ( P < 0.05). The top 10 rearrangements in the repertoire were increased at EX compared with rest ( P < 0.05) and +1H ( P < 0.05). Cross-referencing TCR-β sequences with a public database (VDJdb) revealed that exercise increased the number of clones specific for the most prevalent motifs, including Epstein-Barr virus, cytomegalovirus, and influenza A. We identified 633 unique exercise-responsive T-cell clones that were mobilized and/or egressed in response to exercise. Among these clones, there was an upregulation in genes related to cell death, cytotoxicity, and activation ( P < 0.05). Acute exercise promotes an oligoclonal T-cell repertoire by preferentially mobilizing the most dominant clones, several of which are specific to known viral antigens and display differentially expressed genes indicative of cytotoxicity, activation, and apoptosis.