Document 0741
 DOCN  M9550741
 TI    Inhibition of apoptosis in T cells expressing human T cell leukemia
       virus type I Tax.
 DT    9505
 AU    Copeland KF; Haaksma AG; Goudsmit J; Krammer PH; Heeney JL; Laboratory
       of Viral Pathogenesis, Biomedical Primate Research; Centre, Rijswijk,
       The Netherlands.
 SO    AIDS Res Hum Retroviruses. 1994 Oct;10(10):1259-68. Unique Identifier :
       AIDSLINE MED/95151363
 AB    This study set out to determine whether T cell dysfunction associated
       with HTLV-I led to increased sensitivity of infected cells to apoptosis
       or, owing to their potential to develop ATL, if infected cells would
       become resistant to this process. To test this hypothesis we utilized
       the monoclonal antibody anti-APO-1, which has been demonstrated to
       induce apoptosis in human T cells. Human T cell lines expressing HTLV-I
       showed reduced susceptibility to anti-APO-1-induced apoptosis despite
       expression of high levels of cell surface APO-1. Cell-free supernatant
       of the Tax-expressing cell line C8166 and heat-inactivated supernatant
       of the HTLV-I-producing cell line MT2 transferred increased resistance
       to anti-APO-1 to susceptible Jurkat T cells. Susceptible T cells
       transfected with an HTLV-I Tax-expressing vector or treated with soluble
       Tax protein became less susceptible to anti-APO-1-induced cell death.
       Furthermore, primary human lymphocytes treated with soluble Tax were
       less susceptible to apoptosis induced by anti-APO-1. The protective
       effect of Tax in T cell lines and primary human lymphocytes was reversed
       by the addition of anti-Tax antibodies. Anti-APO-1-induced apoptosis was
       also found to be inhibited in Jurkat cells by the induction of protein
       kinase C (PKC) with 12-O-tetradecanoylphorbol-13-acetate (TPA).
       Resistance to apoptosis conferred by HTLV-I Tax and an active PKC
       pathway may be factors contributing to the survival of dysregulated
       HTLV-I-infected T cells prone to the development of adult T cell
       leukemia.
 DE    Antibodies, Monoclonal/PHARMACOLOGY  Antigens,
       Surface/ANALYSIS/BIOSYNTHESIS/IMMUNOLOGY  *Apoptosis/DRUG EFFECTS  Cell
       Line  Cell Survival  Cells, Cultured  Enzyme Induction  Gene Expression
       Gene Products, tax/*BIOSYNTHESIS  Human  HTLV-I/*PHYSIOLOGY  Protein
       Kinase C/BIOSYNTHESIS  Support, Non-U.S. Gov't
       T-Lymphocytes/IMMUNOLOGY/*PHYSIOLOGY/VIROLOGY  Tetradecanoylphorbol
       Acetate/PHARMACOLOGY  Transfection  JOURNAL ARTICLE

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