The Primary and Memory Immune Response to Epstein–Barr Virus Infection <i>In Vitro</i> is Characterized by a Divergent Production of IL‐1β/IL‐6 and IL‐10

Abstract

Reactivation of latent Epstein-Barr virus (EBV) infection is considered to exert substantial immunomodulating activities. Little is known about EBV's modulating activities on cytokine production upon primary, in contrast to reactivated, infection. Therefore, we investigated the cytokine production of latently infected EBV-positive (EBV-pos) adults upon in vitro EBV stimulation compared to nonimmune age-matched EBV-negative (EBV-neg) donors. Production of interleukin (IL)-1beta and IL-6 was strongly decreased in peripheral blood mononuclear cell (PBMC) cultures of EBV-pos adults; in contrast, IL-10 and IL-1 receptor antagonist exhibited significantly higher levels. As expected, interferon (IFN)-gamma production was almost exclusively observed in EBV-pos donors; it was accompanied by a significantly higher IL-12 synthesis. Experiments employing T cell-depleted PBMC showed similar cytokine levels between EBV-pos and EBV-neg individuals suggesting that reactivation of EBV-specific memory T cells was responsible for the divergent cytokine profiles. Production of viral IL-10 was excluded as a reason for higher IL-10 levels in EBV-pos individuals. In conclusion, our results do not appear to relate to any primary immunological differences between EBV-neg and EBV-pos adults, but show that the EBV-specific memory response to latent EBV infection is characterized by some anti-inflammatory effects. This might be of relevance upon reactivation of latent EBV infection in vivo and provides further evidence that EBV infection acts in an immunomodulating fashion.