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

Tiffany M. Zúñiga, Forrest L. Baker, Kyle A. Smith, Helena Batatinha, Branden Lau, Shane C. Burgess, Michael P. Gustafson, Emmanuel Katsanis, Richard J. Simpson

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose 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. Methods Healthy volunteers completed a graded bout of cycling exercise up to 80% VO2max. 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. Results 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). Conclusions 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.

Original languageEnglish (US)
Pages (from-to)991-1002
Number of pages12
JournalMedicine and science in sports and exercise
Volume55
Issue number6
DOIs
StatePublished - Jun 1 2023

Keywords

  • Exercise Immunology
  • Lymphocytes
  • Scrnaseq
  • T-Cell Diversity
  • Tcr Sequencing
  • Viral Antigens

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

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