Document 0247
 DOCN  M9550247
 TI    Tat-expressing Jurkat cells show an increased resistance to different
       apoptotic stimuli, including acute human immunodeficiency virus-type 1
       (HIV-1) infection.
 DT    9505
 AU    Gibellini D; Caputo A; Celeghini C; Bassini A; La Placa M; Capitani S;
       Zauli G; Institute of Microbiology, University of Ferrara, Italy.
 SO    Br J Haematol. 1995 Jan;89(1):24-33. Unique Identifier : AIDSLINE
       MED/95134677
 AB    Human CD4+ T lymphoblastoid Jurkat cells were stably transfected with
       two different plasmid vectors containing the cDNA of human
       immunodeficiency virus-type 1 (HIV-1) tat gene under the control of
       either the promoter of simian virus 40 (pRPneo/tat) or the long terminal
       repeat region of SL3 murine leukaemia virus (pRPneo/SL3/tat). Both
       pRPneo/tat and pRPneo/SL3/tat Jurkat cell lines showed a constant and
       high production of bioactive Tat in transient co-transfection assays
       with an HIV-1 long terminal repeat (LTR)-chloramphenicol
       acetyltransferase (CAT) reporter plasmid. Tat-positive and
       mock-transfected Jurkat cells were cultured with various cytotoxic
       agents, which have been associated to the progressive loss of CD4
       T-lymphocytes characteristic of HIV-1 disease. In the presence of
       recombinant tumour necrosis factor-alpha (TNF-alpha), anti-fas antibody,
       Leu3a anti-CD4 antibody, the percentage of apoptosis, evaluated in a
       24-72 h short-term assay, was lower (P < 0.05) in tat-positive Jurkat
       cells than in mock-transfected controls. The low susceptibility to the
       cytotoxic activity of TNF-alpha and anti-fas antibody of tat-transfected
       cells was confirmed by counting viable cells up to 15 d of culture.
       Also, recombinant Tat protein was able to prevent the increase of
       apoptosis induced in mock-transfected Jurkat by TNF-alpha. Of note,
       tat-expressing cells showed a better survival with respect to
       mock-transfected control cells even when acutely infected with high
       doses (500,000 cpm of reverse transcriptase) of HIV-1 (strain IIIB) or
       treated with heat-inactivated HIV-1. These data demonstrate that the
       expression of the regulatory HIV-1 Tat protein is able to rescue Jurkat
       lymphoblastoid cells from apoptosis induced by a variety of cytotoxic
       agents. Since Tat protein expression is restricted to the initial phases
       of an active HIV-1 replication, the anti-apoptotic effect of Tat could
       have the physiological significance of selectively protecting HIV-1
       producing cells from death, at least for the time necessary to allow
       virus production and spreading.
 DE    Antibodies, Monoclonal/PHARMACOLOGY  Antigens, CD4/ANALYSIS/IMMUNOLOGY
       Antigens, Surface/ANALYSIS/IMMUNOLOGY  Apoptosis/*GENETICS  CD4-Positive
       T-Lymphocytes/*PATHOLOGY/ULTRASTRUCTURE  *Genes, tat  Human  HIV
       Infections/*GENETICS  HIV-1/*GENETICS  Plasmids/GENETICS  Support,
       Non-U.S. Gov't  Transfection  Tumor Cells, Cultured  Tumor Necrosis
       Factor/PHARMACOLOGY  JOURNAL ARTICLE

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