title: Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans.
abstract: Acute bouts of aerobic exercise are known to mobilize antigen-experienced CD8+ T-cells expressing the cell surface marker of senescence, KLRG1, into the blood. It is not known; however if this is due to a selective mobilization of terminally differentiated T-cells (i.e., KLRG1 +/CD28-/CD57+) or a population of effector memory T-cells (i.e., KLRG1+/CD28+/CD57-) that have not reached terminal differentiation. The aim of this study was to further characterize KLRG1 + T-cells mobilized by acute exercise by assessing the co-expression of KLRG1 with CD28 or CD57 and to determine telomere lengths in the CD4+ and CD8+ T-cell subsets. Nine moderately trained male subjects completed an exhaustive treadmill running protocol at 80%. Blood lymphocytes isolated before, immediately after and 1h after exercise were labelled with antibodies against KLRG1, CD28 or CD57, CD4 or CD8 and CD3 for 4-color flow cytometry analysis. Telomere lengths in CD3+, CD4+ and CD8+ T-cells were determined using Q-PCR. The relative proportion of KLRG1 + cells among the CD8+ T-cells increased by 40% immediately after exercise, returning to baseline 1h later. This was due to a mobilization of KLRG1+/CD28- (61% increase), KLRG1+/CD57+ (56% increase) and to a lesser extent, KLRG1+/CD57- cells (24% increase). Telomeres in CD8+ T-cells displayed an increased relative length immediately after exercise, whereas no change occurred for CD4+ or the overall CD3+ T-cells. In conclusion, the increased frequency of KLRG1 +/CD8+ T-cells in blood after acute exercise is predominantly due to a selective mobilization of terminally differentiated T-cells. The increased relative telomere length in CD8+ T-cells after exercise might indicate that KLRG1+ cells mobilized by exercise are under stress or aberrant signaling-induced senescence (STASIS). We postulate that a frequent mobilization of these cells by acute exercise might eventually allow naïve T-cells to occupy the "vacant" immune space and increase the naïve T-cell repertoire.
authors.affiliation: Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, Texas 77204, USA. rjsimpson@uh.edu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Cormac
authors.initials: C
authors.lastname: Cosgrove
authors.forename: Meng M
authors.initials: MM
authors.lastname: Chee
authors.forename: Brian K
authors.initials: BK
authors.lastname: McFarlin
authors.forename: David B
authors.initials: DB
authors.lastname: Bartlett
authors.forename: Guillaume
authors.initials: G
authors.lastname: Spielmann
authors.forename: Daniel P
authors.initials: DP
authors.lastname: O'Connor
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Pircher
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shiels
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002469:Cell Separation; D016922:Cellular Senescence / Q000276:immunology*; D015444:Exercise; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D010641:Phenotype; D011971:Receptors, Immunologic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016615:Telomere / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis / Q000276:immunology
chemical_list: C113413:KLRG1 protein, human; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D015534:Trans-Activators