title: Cyclosporin abrogates virus-specific T-cell control of EBV-induced B-cell lymphoproliferation.
abstract: 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.
authors.affiliation: Department of Microbiology, University of Saskatchewan, Saskatoon, Canada.
authors.forename: L J
authors.initials: LJ
authors.lastname: York
authors.forename: L F
authors.initials: LF
authors.lastname: Qualtiere
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002461:Cell Line, Transformed; D002999:Clone Cells; D003524:Cyclosporins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects; D012756:Sheep; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D003524:Cyclosporins; D015375:Receptors, Interleukin-2