Here researchers provide evidence for one of the many detrimental consequences of cytomegalovirus (CMV) infection. CMV is a near ubiquitous persistent herpesvirus, present in the majority of the population by the time they reach old age. It is thought responsible for some fraction of the age-related disarray of the immune system, as it cannot be cleared and its presence over the years causes ever more memory cells to be uselessly specialized to track it, leaving ever less room for immune cells capable of taking action. One possible approach to this issue is to destroy the excess memory cells to free up space, possibly coupled with delivering new immune cells via cell therapy, but there is little work taking place on that front, as is true of most potential rejuvenation treatments.
The rapid redeployment of natural killer (NK) cells between the tissues and the peripheral circulation is an archetypal feature of the acute stress response. The response can be evoked using acute bouts of dynamic exercise and is often considered to be an accurate representation of an organism's ability to mount an effective immune response during fight-or-flight scenarios when tissue injury and infection are likely to occur. Acute exercise is associated with increased levels of stress hormones which interact with β-adrenergic receptors (β-AR) on the surface of lymphocytes. NK-cells express more β-AR than other lymphocytes and, as a result, they are the most responsive lymphocyte subset to exercise.
Cytomegalovirus (CMV) is a prevalent beta herpesvirus infecting 50-80% of the US population. We have shown that prior exposure to CMV profoundly impacts the redistribution of lymphocytes to an acute exercise bout. While those with CMV have an augmented redeployment of CD8+ T-cells and γδ T-cells, NK-cell mobilization is dramatically impaired. This blunted NK-cell response appears to be attributable to a CMV-induced accumulation of specific NK-cell subsets that have a lower expression of β2-AR and an impaired ability to produce cyclic AMP in response to in vitro stimulation with the β-agonist isoproterenol. Moreover, those with CMV fail to exhibit exercise-induced enhancements in NK-cell function, indicating that CMV may compromise NK-cell mediated immunosurveillance after an acute bout of strenuous exercise.
In addition to infection history, aging is known to have a profound impact on the cellular response to acute stress and exercise; however, studies investigating the effects of aging on NK-cell exercise responsiveness are lacking. While aging has been reported in some studies to have no effect on NK-cell mobilization with exercise, several of the phenotypic hallmarks of aging overlap with those associated with latent CMV infection in the young. Despite CMV prevalence increasing with age, previous studies have compared NK-cell responses between young and old exercisers without accounting for this confounding variable. We showed recently that CMV was associated with enhanced redeployment of CD8+ T-cells regardless of age, while, conversely, aging impairs the redeployment of γδ T-cells independently of CMV. However, no study to our knowledge has compared NK-cell responses to a single bout of exercise between different age groups while controlling for CMV status. Given that CMV prevalence increases with age and many of the effects of CMV mirror those attributable to aging, it is important to resolve the effects of age and CMV infection on the frequency and exercise responsiveness of distinct NK-cell subsets.
The aim of this study was to determine if latent CMV infection blunts the redeployment of NK-cells to a single exercise bout in older individuals as it does in the young and to delineate the effects of age and CMV on the redeployment of discrete NK-cell subsets. We show here that CMV has a potent blunting effect on exercise-induced NK-cell mobilization in both younger (23-39 yrs) and older (50-64 yrs) subjects with the greatest mobilization being seen in the CMV-negative older group.