Latent CMV And EBV Infections And The Mobilization Of Viral-specific And Senescent T-cells With Exercise

Abstract

Reactivating latent viruses cause senescent T-cells to accumulate within the so-called "immune space", reducing the naïve T-cell repertoire and increasing host infection risk. Although senescent T-cells (i.e. KLRG1+/CD57+) are mobilised into the blood by acute exercise, the impact of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on this response is unknown. It remains to be determined also if the mobilized cells react with epitopes of the CMV or EBV virus in those infected. PURPOSE: To determine: (1) if CMV and EBV specific T-cells are mobilised into blood in response to acute exercise; and (2) the impact of latent CMV and EBV infections on the exercise-responsiveness of senescent T-cells. METHODS: Twenty-four healthy males (age 28.5 ± 5) completed a 30-min cycling protocol at 85% of maximum power. Mononuclear cells were isolated from blood before, immediately after and 1hour after exercise and labelled with MHC class I Pentamers specific to CMV (pp65) or EBV (LMP-2) and anti CD3 and CD8 antibodies. Naïve (KLRG1-/CD28+/CD57-), effector-memory (KLRG1+/CD28+/CD57-) and senescent (KLRG1+/CD28-/CD57+) phenotypes were determined on pentamer positive and negative CD8+ T-cells by flow cytometry. ELISA tests were used to determine CMV and EBV serostatus. RESULTS: Exercise increased the numbers of CMV and EBV-specific T-cells by 158% and 200% respectively (p<.01), and altered the proportions of senescent (+44%) and naïve (-20%) CD8+ T-cells (p<.05). CMV seropositive (n = 10) had a greater (+136%; p<.01) proportion of senescent and a lower (-33%; p<.01) proportion of naïve CD8+ T-cells compared to seronegative (n= 14), and demonstrated a blunted senescent T-cell response to exercise (+38% vs +51%; p<.01). Senescent markers on both CMV and EBV-specific T-cells increased with exercise (+53% and +76% respectively; p<.05). EBV serostatus did not influence the proportions or exercise response of the CD8+ T-cell populations (p>.05). CONCLUSION: CD8+ T-cells specific to CMV and EBV are mobilized into blood with acute exercise; however, the relative exercise responsiveness of senescent T-cells is blunted with CMV infection. Future work should determine the fate of the mobilized senescent cells and the potential impact that exercise might have on creating "immune space" in those infected with CMV.