PRODUCTION OF INFLAMMATORY CYTOKINES BY EPSTEIN-BARR-VIRUS (EBV)-INFECTED LYMPHOBLASTOID CELL-LINES SPONTANEOUSLY ORIGINATED FROM THE PERIPHERAL-BLOOD OF PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) INFECTION

In this study we have raised spontaneous Epstein-Barr virus (EBV)-posi tive lymphoblastoid cell lines (LCL) from the peripheral blood of huma n immunodeficiency virus (HIV)-infected individuals and of control pat ients with primary EBV infections. These LCLs were also raised in the presence of the viral inhibitor phosphonoformate (PFA); under these co nditions, the in vitro infection of bystander B lymphocytes with EBV r eleased in culture by in vivo infected B cells is inhibited. Thus, the latter LCLs are likely to represent the progeny of B cells latently i nfected by EBV in vivo. The LCLs raised in the presence or absence of PFA had the same phenotypic features, type of EBV latency, and growth pattern irrespective of whether they had been raised from HIV-seroposi tive individuals or patients with primary EBV infections or had been g enerated by infecting normal B cells in vitro. Studies on the producti on of inflammatory cytokines were conducted by Northern blotting or by determining the cytokine concentrations in the cell supernatants by i mmunoassays or bioassays. Three of eight LCLs from HIV-seropositive pa tients released TNF alpha and 5/5 released TNF beta, IL6 was present i n the supernatants of 1/8 LCLs, and IL1 alpha and IL1 beta were not de tected in any culture supernatant. No differences were noticed in the patterns of cytokine secretion among the LCLs from HIV-seropositive pa tients and in those raised from patients with primary EBV infections o r obtained by infecting normal B cells in vitro with EBV. It is tempti ng to speculate that abnormally expanded EBV-harboring B cells in HIV- seropositive patients may participate in the pathogenesis of certain c linical manifestations by releasing inflammatory cytokines; some of th ese cytokines might also contribute to the in vivo spreading of HIV in fection. However, the spontaneous LCLs from HIV-seropositive individua ls do not display abnormal features compared to latently HIV-infected LCLs from other sources despite the high frequency of EBV-driven lymph oproliferative disorders observed in AIDS patients. (C) 1995 Academic Press, Inc.