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Natural killer (NK) cells play a critical role in the host defense against herpesviruses. Although herpesviruses are ubiquitous in human populations, only a minority of people experience severe recurrent infections. We hypothesize that uncharacterized NK cell functional deficits predispose individuals to more significant or frequent herpesvirus infections and reactivations. To investigate this hypothesis, we broadly analyzed NK cell phenotype and functional responses in a cohort of predominantly pediatric patients with recurrent and/or severe herpesvirus infections and compared them to a healthy control population. Our results identified no global differences in cytolysis, degranulation, interferon-γ production, or surface receptor upregulation following cytokine stimulation. However, abnormal NK cell functional responses were observed in nearly one-third of patients (including 3 with hyporesponsiveness to activating signals and 1 with markedly decreased CD11b expression associated with reduced cytotoxicity and degranulation), which might contribute to those individuals' susceptibility to herpesvirus infections.

Natural Killer Cell Functional Defects in Pediatric Patients With Severe and Recurrent Herpesvirus Infections