Epstein-Barr virus latently infects most normal adult individuals worldwide. The mechanisms by which this occurs are incompletely understood. A critical role for T cell immunity is suggested by the observation that severe T cell immunodeficiency is associated in vivo with the occurrence of polyclonal and oligoclonal proliferations of B lymphocytes naturally infected with EBV. In vitro, removal or inactivation of T lymphocytes results in the generation of EBV- immortalized cell lines. T cell specific cytotoxicity, natural cytotoxicity, suppression and secretion of inhibitory molecules have all been shown to inhibit EBV-infected B cells in vitro and are believed to contribute to their control in vivo. In the present study, T-lymphocytes were found to proliferate in response to cell-free supernatants of EBV-immortalized B cells and to deplete EBVimmortalized cells of the growth factors they require for autocrine growth. Interleukin-6 was found to be one of the autocrine growth factors produced by EBV-immortalized B cells that T cells utilize. As a consequence of T cell utilization of growth factors produced by EBV-immortalized B cells and required by the virally infected cells for continuous growth, B cell suppression occurs. Thus, T cell competition for growth factors may represent an important and novel regulatory mechanism for maintenance of EBV latency.
