FREQUENT EXPRESSION OF INTERLEUKIN-10 BY EPSTEIN-BARR VIRUS-HARBORINGTUMOR-CELLS OF HODGKINS-DISEASE

Tumor cells of Epstein-Barr virus (EBV)-associated Hodgkin's disease ( HD) express the viral protein, latent infection membrane protein-1 (LM P1), but evade cytotoxic responses normally directed at this antigen. We tested whether local production of the immunoregulatory interleukin s (IL)-4 and -10 may have a role in this process. IL-4 RNA was not det ectable in any of the HD cases. By contrast, isotopic in situ hybridiz ation and correlation with the presence of EBV gene products showed si gnificantly higher proportions of cases with IL-10 expressing tumor ce lls in LMP1-positive (17 of 26, 66%) as compared with LMP1-negative HD cases (six of 37, 16%). Absence of EBV BCRF1 RNA indicated that the t ranscripts originated from the cellular IL-10 gene. Similarly, an asso ciation between IL-10 expression and EBV-infection of tumor cells was found in AIDS-related malignant non-Hodgkin lymphomas (ARL). Very smal l proportions of EBV-infected cells, mainly blasts, expressed IL-10 in infectious mononucleosis tonsils, Thus, although not entirely exclusi ve to EBV-positive cases, IL-10 expression is frequently associated wi th EBV-infection in HD and ARL and appears to be upregulated by EBV, m ost likely through LMP1. In view of the established inhibitory effects of IL-10 on cell mediated immunity, it is suggested that IL-10 expres sion may contribute to evasion of LMP1-positive cells from cytotoxicit y directed at viral antigens. (C) 1996 by The American Society of Hema tology.