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.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Intramural Research (Z01)
Project #
1Z01BD004003-04
Application #
3792492
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost