Impact Of CMV And EBV Infections On The Exercise-induced Mobilization Of Nk-cells And γδ T-cells

Abstract

PURPOSE: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infect 60% and 80% of the US population, respectively. These persistent viruses compromise immunity to novel pathogens by increasing the frequency of senescent CD8+ T-cells in the periphery; however, less is known about their effects of on the phenotype characteristics of other cytotoxic lymphocytes, such as NK-cells and γδ T-cells. As cytotoxic lymphocytes are preferentially mobilized into the blood in response to acute exercise, we examined the impact of latent CMV and EBV infections on the phenotype characteristics and exercise-responsiveness of NK-cells and γδ T-cells. METHODS: 22 healthy males (Age: 28 ± 5 yrs) completed a 30-min cycling protocol at 85% of maximum power. Lymphocytes isolated from whole blood before, immediately after, and 1-hour after exercise were labeled with monoclonal antibodies to identify CD3-/CD56+ NK-cells and their cell-surface expression of KLRG1, CD57, CD8, and CD158a by flow cytometry. Additionally, CD4+ and CD8+ T-cells were assessed for expression of KLRG1, CD56, and γδ-TCR. ELISA was used to determine CMV and EBV serostatus. Exercise and serostatus main effects, and exercise x serostatus interaction effects, were detected using linear mixed models. RESULTS: CMV infection is associated with a blunted exercise response of NK-cells (+260% vs. +78%; p<0.001) and a lower proportion of NK-cells expressing the inhibitory receptors KLRG1 (53% vs. 44%; p<0.05) and CD158a (14% vs. 8%; p<.05). Higher proportions of cytotoxic CD8+ NK-cells were found with EBV infection (42% vs. 31%; p<.05), but EBV did not affect the relative response of these cells to exercise. Higher proportions of cytotoxic CD56+/CD8+ (12% vs. 18%; p<.01) and effector-memory KLRG1+/CD8+ T-cells (38% vs. 49%; p<.01) were found in the CMV infected, who also exhibited a greater relative mobilization of KLRG1+/CD8+ T-cells with exercise (+26% vs +33%; p<.01). CMV and EBV infection did not influence the frequency of CD4+ or CD8+ γδ T-cells or their response to exercise. CONCLUSION: CMV infection is associated with a downregulation of NK-cell inhibitory receptors and a blunted NK-cell mobilization with exercise. This implies that NK-cell immune surveillance may be impaired in CMV infected individuals both at rest and following an acute bout of exercise.