NK-cells have an impaired response to acute exercise and a lower expression of the inhibitory receptors KLRG1 and CD158a in humans with latent cytomegalovirus infection

NM-cells and gamma delta T-cells are cytotoxic effectors of the immune system that are preferentially mobilized into the blood compartment in response to acute stress and exercise. While infection history is known to alter the phenotype and exercise-responsiveness of CD8+ T-cells, the influence of latent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections on the phenotypes and exercise-responsiveness of NM-cells and gamma delta T-cells are unknown. Twenty healthy males (age: 28.4 +/- 5.4 years) cycled for 30 min at 85% peak power. Blood lymphocytes isolated before, immediately after, and 1 h after exercise were surface stained for CD3, CD4, CD8, CD56, CD57, CD158a, KLRG1, and gamma delta-TCR antigens by four-color flow cytometry. CMV and EBV serostatus (pos/neg) was determined by ELISA. CMVpos had lower proportions of NM-cells expressing inhibitory receptors (KLRG1+ and CD158a+) and higher proportions of terminally differentiated NM-cells (KLRG1-/CD57+) compared to CMVneg. CMVpos mobilized far fewer (132 cells/mu L vs. 245 cells/mu L) NM-cells in response to exercise despite having similar baseline NM-cell counts and physiological responses to exercise as CMVneg, although terminally differentiated NM-cells were equally responsive to exercise regardless of CMV serostatus (p = 0.658). EBVpos had higher proportions of CD8+ NM-cells, but cellular responses to exercise were not influenced by EBV. The frequency and exercise-responsiveness of gamma delta T-cells was not affected by CMV or EBV serostatus (p > 0.05). In conclusion, latent CMV infection is associated with lowered numbers of NM-cells expressing inhibitory receptors and a blunted mobilization of NM-cells in response to acute exercise. This may indicate a compromised immune response to "fight-or-flight" situations in those infected with CMV. (C) 2011 Elsevier Inc. All rights reserved.