No abstract

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.

Aging is associated with a dysfunctional endothelial phenotype as well as reduced angiogenic capabilities. Exercise exerts beneficial effects on the cardiovascular system, possibly by increasing/maintaining the number and/or function of circulating angiogenic cells (CACs), which are known to decline with age. However, the relationship between cardiorespiratory fitness (CRF) and age-related changes in the frequency of CACs, as well as the exercise-induced responsiveness of CACs in older individuals, has not yet been determined. One-hundred seven healthy male volunteers, aged 18-75 yr, participated in study 1. CRF was estimated using a submaximal cycling ergometer test. Circulating endothelial progenitor cells (EPCs), angiogenic T cells (T), and their chemokine (C-X-C motif) receptor 4 (CXCR4) cell surface receptor expression were enumerated by flow cytometry using peripheral blood samples obtained under resting conditions before the exercise test. In study 2, 17 healthy men (8 young men, 18-25 yr; 9 older men, 60-75 yr) were recruited, and these participants undertook a 30-min cycling exercise bout at 70% maximal O consumption, with CACs enumerated before and immediately after exercise. Age was inversely associated with both CD34 progenitor cells ( r = -0.140, P = 0.000) and T ( r = -0.176, P = 0.000) cells as well as CXCR4-expressing CACs (CD34: r = -0.167, P = 0.000; EPCs: r = -0.098, P = 0.001; T: r = -0.053, P = 0.015). However, after correcting for age, CRF had no relationship with either CAC subset. In addition, older individuals displayed attenuated exercise-induced increases in CD34 progenitor cells, T, CD4, T, and CD8CXCR4 T cells. Older men display lower CAC levels, which may contribute to increased risk of cardiovascular disease, and older adults display an impaired exercise-induced responsiveness of these cells. NEW & NOTEWORTHY Older adults display lower circulating progenitor cell and angiogenic T cell counts compared with younger individuals independently of cardiometabolic risk factors and cardiorespiratory fitness. Older adults also display impaired exercise-induced mobilization of these vasculogenic cells.

This study examined the effects of intensive, moderate and downhill treadmill running on blood lymphocyte expression of adhesion/activation (AA) molecules. Trained subjects completed three treadmill-running protocols of identical duration: (1) an intensive protocol at 80% VO2max to volitional exhaustion, (2) a moderate protocol at 60% VO2max and (3) a -10% downhill (eccentric) protocol at 80% VO2max. Blood samples were taken before, immediately after, 1 and 24 h after exercise. Isolated lymphocytes were assessed for expression of the AA molecules CD54, CD18 and CD53 by flow cytometry. Lymphocyte counts increased immediately after all running protocols. Lymphocytopenia was observed 1 h after the intensive and eccentric protocols only. Plasma creatine kinase increased 24 h after the downhill protocol only. Increases in the number and percentage of CD54+, CD18bright and CD53bright lymphocytes were observed immediately after the intensive and eccentric protocols, with the numbers falling below pre-exercise values at 1 h post-exercise for all protocols. No differences were found between the intensive protocol and the eccentric protocol at the same relative intensity. Analysis of lymphocyte subsets showed that the total number of CD3+, CD4+, CD8+ and CD56+ lymphocytes increased after the intensive protocol before falling below pre-exercise values at 1 h post-exercise. A relatively greater mobilisation of CD56+ and CD8+ cells accounts for the changes in CD54+, CD18bright and CD53bright cell populations. Lymphocytes that enter and exit the circulation following exercise express high levels of AA molecules, which may mediate extravasation and post-exercise lymphocytopenia. This effect appears to be influenced by exercise intensity and not muscle damage.

Repeated bouts of prolonged exercise induce short-term reductions in diastolic filling and a cumulative decrease in systolic function, yet these alterations seem to have minimal clinical or functional impact. Elevated cTnT after the initial bout, but not thereafter, may represent an adaptive response to prolonged exercise.