Cyclosporine-induced apoptosis in CD4+ T lymphocytes and computer-simulated analysis: modeling a treatment scenario for HIV infection.
Cyclosporine A (CsA) is a potent immunosuppressive drug which interferes in vitro and in vivo with T-cell function. CsA has been shown to arrest T-cell maturation intrathymically and to inhibit T-cell proliferation. In this study, we demonstrate that CsA induces apoptosis in the canine CD4+ CD8- T-lymphocyte cell line 401 in a dose- and time-dependent fashion. Similar results could also be obtained from human peripheral blood lymphocytes. Apoptosis is observed within 4 hours after CsA application and is not prevented by excessive addition of ConA supernatant as a source of interleukins. The induction of apoptosis in CD4+ T lymphocytes suggests a possible treatment option for human immunodeficiency virus (HIV) infections, since the major target population for the HIV would be ablated at short term. A computer-simulated analysis with the "Cybermouse" HIV model confirmed that the virus would eventually disappear and HIV-infected macrophages would also be substantially reduced if CsA were given in combination with drugs which block viral replication (3'-azido 3'-deoxythymidine or 2',3'-dideoxycytidine). This treatment scenario could be applied under controlled conditions and with supportive patient care. A further review of the literature also suggests the positive impact of CsA treatment on the progression and outcome of AIDS-related mortality.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D003198:Computer Simulation; D016572:Cyclosporine / Q000494:pharmacology*; D004285:Dogs; D006131:Growth Inhibitors / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008954:Models, Biological
D006131:Growth Inhibitors; D016572:Cyclosporine