       Document 0202
 DOCN  M9620202
 TI    Cyclosporine-induced apoptosis in CD4+ T lymphocytes and
       computer-simulated analysis: modeling a treatment scenario for HIV
       infection.
 DT    9602
 AU    Huss R; Hoy CA; Ottinger H; Grosse-Wilde H; Deeg HJ; Clinical Research
       Division, Fred Hutchinson Cancer Research; Center, Seattle, WA, USA.
 SO    Res Immunol. 1995 Feb;146(2):101-8. Unique Identifier : AIDSLINE
       MED/96100666
 AB    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.
 DE    Animal  Apoptosis/DRUG EFFECTS/*IMMUNOLOGY  Cell Line  *Computer
       Simulation  Cyclosporine/*PHARMACOLOGY  CD4-Positive T-Lymphocytes/*DRUG
       EFFECTS/IMMUNOLOGY  Dogs  Growth Inhibitors/PHARMACOLOGY  Human  HIV
       Infections/*DRUG THERAPY  Lymphocyte Depletion  Lymphocyte
       Transformation/DRUG EFFECTS  *Models, Biological  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE  REVIEW  REVIEW OF
       REPORTED CASES

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

