Type 2 cytokines predominate in the human CD4+T-lymphocyte response to Epstein-Barr virus nuclear antigen 1

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that persistentl y infects 85% of the adult population worldwide. In this report, we examine the proliferative response and cytokine secretion profile of CD4(+) T lymp hocytes from a panel of unrelated EBV-positive donors against two EBV laten t antigens, EBNA1 and EBNA3C. Substantial proliferative responses by CD4(+) lymphocytes mere demonstrated to both antigens in multiple, randomly selec ted donors. Surprisingly, we observed a striking and consistent difference in cytokine response to EBNA1 and EBNA3C. EBNA1-specific CD4(+) T lymphocyt es from multiple unrelated donors preferentially produced type 2-like cytok ines in response to antigenic stimulation, while the response to EBNA3C was a characteristic type 1 response, The implications of these findings for E BV persistence and the development of EBV-associated malignancies are discu ssed.