Author(s): STEPHEN, L., WRIGHT, G., MUGGERIDGE, D., GORDON, A., CHANDRAKUMAR, V., ROSS, M. , Institution: HERIOT-WATT UNIVERSITY, Country: UNITED KINGDOM, Abstract-ID: 2558

INTRODUCTION:
T-cells are a key part of the adaptive immune system, whose primary role is to combat infection. However, T-cells also play a vital role on non-immune functions such as tissue repair and maintenance. A subset of T-cells which express the adhesion receptor, CD31 (platelet endothelial cell adhesion molecule; PECAM) are reported to possess angiogenic properties (Hur et al., 2007). These cells have been termed ‘angiogenic’ T-cells (TANG). With advancing age, our T-cell profiles are known to change towards a more pro-inflammatory phenotype, however high levels of cardiorespiratory fitness (CRF) can attenuate this immunological ageing, and therefore may alleviate any age-related effects on TANG cells. Therefore, this study aimed to determine whether CRF is protective against the age-related changes in TANG cell number and angiogenic vascular endothelial growth factor (VEGF)-A expression.
METHODS:
Healthy males (n=32, 18-30yrs & 50-65yrs, BMI<30 kg·m2) were recruited for this study. Participants reported to the Human Performance Laboratory after an overnight fast. A small blood sample was taken, and peripheral blood mononuclear cells (PBMCs) were isolated using density gradient centrifugation. Participants underwent a V.O2max test on an electronically braked cycle ergometer (Lode Corival, Lode B.V., Netherlands) with simultaneous breath-by-breath gas analysis (Cortex Metalyzer, Germany). V.O2max was defined as an RER>1.15, plateau in oxygen consumption and within 10 beats per minute of their age predicted maximum heart rate. PBMCs were used to quantify TANG cells (CD3+CD31+, CD3+CD4+CD31+, CD3+CD8+CD31+) along with the expression of VEGF-A (angiogenic growth factor) and C-X-C chemokine receptor type 4 (CXCR4) (a key chemokine receptor involved in cell migration) using flow cytometry (BD FACSCelesta, BD Biosciences). After data acquisition, data were analysed using Flow Logic (FlowLogic Version 8.7, FlowLogic, Australia).
RESULTS:
VEGF-A expression was significantly greater in CD3+CD31+ T-cells (TANG) than CD3+CD31- T-cells (13097 ± 10942 AU vs 12424 ± 11156 AU respectively, t = 2.390, p = 0.024). However, there was no difference in CXCR4 expression between CD3+CD31+ and CD3+CD31- T-cells (41 ± 16% vs. 48 ± 21%, t = 1.521, p = 0.149). Older adults demonstrated a significantly lower proportion of CD4+ T-cells expressing CD31, with no other alterations in CD31+ T-cell subsets. Moreover, TANG cells (all 3 defined subsets) from older adults displayed greater VEGF-A content than CD31+ T-cells from younger individuals, indicative of a hyper-inflammatory response. VO2max was not a significant covariate, and thus did not affect the age-induced alterations in TANG T-cell number, VEGF-A or CXCR4 expression.
CONCLUSION:
In conclusion, older people display a lower proportion of CD4+CD31+ TANG cells and greater VEGF-A expression across all TANG subsets, which may reflect T-cell phenotypic shifts from naïve to differentiated, pro-inflammatory phenotypes with advancing age.