High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects.
Clonal expansion of T lymphocytes in response to antigenic stimulation is a fundamental process of adaptive immunity. As a consequence of clonal expansion, some T lymphocytes acquire a senescent phenotype, fail to replicate in response to further antigenic stimulation, and express the killer cell lectin-like receptor G1 (KLRG1) and/or CD57. Physical exercise elicits a mobilization of large numbers of T lymphocytes into the bloodstream from peripheral lymphoid compartments, but the frequency of senescent cells in the mobilized population is not known. Eight male runners (age: 29 +/- 9 yr; maximal O2 uptake 62 +/- 6 ml x kg(-1) x min(-1)) performed an intensive treadmill-running protocol at 80% maximal O2 uptake to volitional exhaustion. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry. The percentage of all CD3+ T lymphocytes expressing KLRG1 and CD57 increased with exercise (P < 0.01). The change in T-lymphocyte KLRG1 expression was attributed to both CD4+ and CD8 bright T cells, with the relative change being greater for the CD8 bright population (P < 0.01). Mobilized T-lymphocyte populations expressing KLRG1 and CD57 appeared to extravasate the peripheral blood compartment after 1 h of recovery. In conclusion, T lymphocytes with a senescent phenotype are mobilized and subsequently removed from the bloodstream in response to acute high-intensity exercise. This suggests that T lymphocytes contained within the peripheral lymphoid compartments that are mobilized by exercise are likely to be at a more advanced stage of biological aging and have a reduced capacity for clonal expansion than blood-resident T cells.
Simpson
Richard J
RJ
Biomedicine and Sports Science Research Group, School of Life Sciences, Napier University, Edinburgh, Scotland EH10 5DT, UK. r.simpson@napier.ac.uk
Florida-James
Geraint D
GD
Cosgrove
Cormac
C
Whyte
Greg P
GP
Macrae
Scott
S
Pircher
Hanspeter
H
Guy
Keith
K
D000328:Adult; D018106:CD28 Antigens / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018959:CD57 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D016922:Cellular Senescence; D015331:Cohort Studies; D015444:Exercise / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D019041:L-Selectin / Q000032:analysis; D037181:Lectins, C-Type / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D008297:Male; D018763:Muscle Fatigue / Q000276:immunology*; D010101:Oxygen Consumption; D011971:Receptors, Immunologic; D013997:Time Factors; D015534:Trans-Activators / Q000032:analysis
D018106:CD28 Antigens; D017252:CD3 Complex; D018959:CD57 Antigens; C113413:KLRG1 protein, human; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D015534:Trans-Activators; D019041:L-Selectin; D017493:Leukocyte Common Antigens