LOCAL SUPPRESSION OF EPSTEIN-BARR-VIRUS (EBV)-SPECIFIC CYTOTOXICITY IN BIOPSIES OF EBV-POSITIVE HODGKINS-DISEASE

Epstein-Barr virus (EBV)-positive Hodgkin's and Reed-Sternberg (HRS) cells express the virus-encoded latent membrane proteins LMP1 and LMP2 that could serve as rejection targets in Hodgkin's disease (HD). To examine whether EBV-triggered reactivities can be detected in the tumor, we have compared cytokine mRNA expression, cell phenotype, and cytotoxic activity in biopsies from 8 EBV-carrying and 6 EBV(-) HD patients. Neither the pattern of lymphokine production nor the cell phenotype of the in vivo-activated interleukin-2-responding populations provided a clear discrimination between EBV(+) and EBV(-) cases. HLA class I-restricted EBV-specific cytotoxicity was shown in interleukin-2-dependent cultures from 3 of 3 EBV(-) tumors, whereas cultures from 6 of 6 EBV(+) tumors were either noncytotoxic or exerted LAK-type cytotoxicity. EBV-specific cytotoxic T lymphocyte precursors were present in the blood of 1 patient carrying an EBV(+) tumor. The results suggest that a tumor-associated suppression of EBV-specific T-cell responses may play an important role in the pathogenesis of EBV(+) HD. (C) 1995 by The American Society of Hematology.