Analysis of Tonsillar NK Cell Markers in Pediatric Epstein–Barr Virus (EBV) Asymptomatic Infection and EBV-Associated Hodgkin Lymphoma

In Argentina, a high incidence of EBV-associated lymphomas was demonstrated in young children. Natural killer (NK) cells, particularly, IFN-γ-producing CD56bright NK cells, have been reported to play a key role in asymptomatic EBV infection in children, restricting viral-mediated transformation. In order to analyze NK cell characteristics in children with primary and persistent EBV infection, along with EBV+ Hodgkin lymphoma (HL) from Argentina, a cohort of EBV-infected pediatric patients was analyzed. A scarcity of CD56+ cells, as an indirect marker of NK cells, across all tonsillar samples and pediatric classical Hodgkin lymphoma cases was observed, with no significant differences according to EBV status. In primary infection, CD56+ cells showed a positive correlation with IFNγ+ cells, suggesting a role in early antiviral responses. Flow cytometry revealed an increased proportion of CD56bright NK cells in EBV-infected children, particularly in cases expressing latency II/III antigens. A significantly higher IFN-γ production was observed in CD56bright cells in children with primary infection compared with healthy carriers, along with an inverse correlation between IFN-γ production and CD56bright cells in healthy carriers. These findings suggest that NK cells may contribute to immune control predominantly during primary infection, whereas their role appears limited in healthy carriers and in EBV-associated Hodgkin lymphoma.