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Cyclosporin abrogates virus-specific T-cell control of EBV-induced B-cell lymphoproliferation
1Department of Microbiology, University of Saskatchewan, Saskatoon, Canada.
Renal and cardiac recipients undergoing aggressive immunosuppressive therapy with cyclosporin A have been reported to have unusually high incidences of Epstein-Barr virus (EBV) genome-positive lymphomas. T cells have been shown to be of critical importance in controlling the lymphoproliferative potential of the EB virus. EBV-specific T cell clones were generated in vitro by repeated antigenic restimulation in the presence of interleukin-2 (IL-2). These virus-specific cells were used to study cyclosporin A's effect on their activation, proliferation and cytotoxic function, and the possible abrogation of the cell's ability to control virus-induced lymphoproliferation. In this study, we show that cyclosporin A does not interfere with antigen recognition, since the T cell cytotoxic potential is unchanged. However, cyclosporin A induces a dose-dependent reduction in membrane IL-2 receptor expression which consequently limits the proliferation of the antigen-activated cell. This may translate in vivo to an insufficient expansion of the cytotoxic T cells which controls the outgrowth of the EBV-infected B cell.
Renal and cardiac recipients undergoing aggressive immunosuppressive therapy with cyclosporin A have been reported to have unusually high incidences of Epstein-Barr virus (EBV) genome-positive lymphomas. T cells have been shown to be of critical importance in controlling the lymphoproliferative potential of the EB virus. EBV-specific T cell clones were generated in vitro by repeated antigenic restimulation in the presence of interleukin-2 (IL-2). These virus-specific cells were used to study cyclosporin A's effect on their activation, proliferation and cytotoxic function, and the possible abrogation of the cell's ability to control virus-induced lymphoproliferation. In this study, we show that cyclosporin A does not interfere with antigen recognition, since the T cell cytotoxic potential is unchanged. However, cyclosporin A induces a dose-dependent reduction in membrane IL-2 receptor expression which consequently limits the proliferation of the antigen-activated cell. This may translate in vivo to an insufficient expansion of the cytotoxic T cells which controls the outgrowth of the EBV-infected B cell.