A 10 km time trial running bout acutely increases the number of angiogenic T cells in the peripheral blood compartment of healthy males

Abstract

What is the central question of the study? Are CD31 angiogenic T (T ) cells preferentially mobilized in response to acute exercise? What is the main finding and its importance? Our study reveals that T cells are redistributed into the circulation in response to acute strenuous exercise, but to a lesser extent than CD31 T cells. Of the T cells mobilized, T cells expressing CXCR4 show greater redistribution compared with CXCR4 T cells. Stromal-derived factor 1-α does not appear to play a role in the redistribution of T cells expressing CXCR4. The results suggest that a single bout of strenuous exercise might provide a short vasculogenic window, which could benefit the vascular system by redistributing CD31 T cells. CD31 T cells have been documented to possess vasculogenic properties and have been termed 'angiogenic T cells' (T cells). No study to date has fully characterized the effect of acute exercise on T cells. Twelve male participants aged 24-45 years undertook a running 10 km time trial, with peripheral blood samples taken before, immediately after and 1 h postexercise for quantification of T cells and subsequent CXCR4 cell surface expression by flow cytometry. The T cells demonstrated a 102% increase in number in the peripheral circulation immediately postexercise compared with pre-exercise levels, followed by a large egress (50%) from the circulation in total T cells 1 h postexercise. This was due to changes in both CD4 and CD8 T cells, with CD8 T cells displaying greater ingress (123%) and egress (52%) compared with CD4 T cells (ingress, 83%; egress, 37%). The cell surface expression intensity of CXCR4 was affected only on CD8 T cells, with a significant increase in cell surface expression immediately postexercise versus pre-exercise levels. The CD31 T cells displayed greater redistribution than CD31 T cells (119 versus 102%). CXCR4-expressing T cells showed greater response to acute exercise than CXCR4 cells, which was accompanied by large changes in CXCR4 ligand SDF-1α. The results show that acute exercise increases T cells in the circulation in response to an acute exercise stressor. Additionally, CXCR4 cell surface expression appears to be increased in response to exercise, which may result from the direct upregulation of CXCR4 on the T-cell surface or could be due to CD31 T cells being redistributed into the blood expressing greater levels of CXCR4.

Older men display elevated levels of senescence-associated exercise-responsive CD28nullangiogenic T cells compared with younger men

“…A single bout of exercise is known to stimulates the movement of EPCs into the peripheral blood compartment in the postexercise period (van Craenenbroeck et al 2008;Ross et al 2014Ross et al , 2018, which may offer a vasculogenic window of adaptation. Previous studies have also observed redistribution of T ANG cells into the circulation with a single bout of exercise, in both young and older men (Ross et al 2016(Ross et al , 2018. This T-cell response is not uncommon, as many T-cell subsets increase in circulation in response to acute exercise stimuli, such as naive T cells (T NA € IVE ), cytotoxic T cells (T CYTOTOXIC ), and regulatory T cells (T REG ) (Brown et al 2014;Spielmann et al 2014;Ingram et al 2015;Clifford et al 2017).…”

“…Previous studies have also observed redistribution of T ANG cells into the circulation with a single bout of exercise, in both young and older men (Ross et al. , ). This T‐cell response is not uncommon, as many T‐cell subsets increase in circulation in response to acute exercise stimuli, such as naive T cells (T NAÏVE ), cytotoxic T cells (T CYTOTOXIC ), and regulatory T cells (T REG ) (Brown et al.…”

“…Our lab has previously shown that exercise significantly increases the number of circulating T ANG cells (Ross et al. ), and older adults display reduced resting and exercise‐induced mobilization of T ANG cells into the circulation in response to an exercise bout (Ross et al. ).…”

“…Interestingly, we also show that in the young population (18-25 years) that there were no differences in the response of CD28 null and CD28 + T ANG cells; however, in the older population (60-75 years), there was a greater responsiveness of CD28 null than CD28-expressing CD8 + T ANG cells. Our lab has previously shown that exercise significantly increases the number of circulating T ANG cells (Ross et al 2016), and older adults display reduced resting and exercise-induced mobilization of T ANG cells into the circulation in response to an exercise bout (Ross et al 2018). Reductions in basal T ANG cells in older adults may be due to thymic involution (Simpson 2011); however, we do observe an increase in CD28 null T ANG cells in the older population.…”

“…Total blood differential leukocyte counts were determined using an automated hematology analyzer (XS 1000i, Sysmex, UK). Peripheral blood mononuclear cells (PBMC) were isolated using density gradient centrifugation as described elsewhere (Ross et al 2016). PBMCs were stained with anti-CD3-FITC, anti-CD31-APC, and anti-CD28-PE-Cy5 antibodies (all BD Biosciences, UK), with subanalysis of T-cell subsets using anti-CD4-PE (Miltenyi-Biotec, Germany) and anti-CD8-PE (BD Biosciences, UK) antibodies to determine CD4 + and CD8 + T ANG cells.…”