       Document 0648
 DOCN  M9620648
 TI    Differential susceptibility to monomeric HIV gp120-mediated apoptosis in
       antigen-activated CD4+ T cell populations.
 DT    9602
 AU    Tuosto L; Montani MS; Lorenzetti S; Cundari E; Moretti S; Lombardi G;
       Piccolella E; Department of Cellular and Developmental Biology,
       University La; Sapienza, Rome, Italy.
 SO    Eur J Immunol. 1995 Oct;25(10):2907-16. Unique Identifier : AIDSLINE
       MED/96062044
 AB    To support the hypothesis that indirect mechanisms mediated by viral
       products like the HIV envelope glycoprotein gp120 could be responsible
       for T lymphocyte depletion in HIV infection, we developed a system in
       which the impairment of T cell functions could be investigated in vitro.
       In particular, we characterized the conditions that allow T lymphocytes
       repeatedly stimulated with an antigen to be sensitive or resistant to
       gp120-mediated apoptotic signals. To achieve this goal, a panel of
       antigen-specific CD4+ T cell clones and primary CD4+ T lymphocytes were
       treated for 2 and 18 h with saturating amounts of monomeric gp120
       (without cross-linking with specific antibodies) and antigen-driven T
       cell proliferation and apoptosis were analyzed. We show that monomeric
       gp120 induces apoptosis only in T lymphocytes repeatedly stimulated with
       the antigen, that primary T lymphocytes are resistant to programmed cell
       death mediated by monomeric gp120, but are sensitive to anti-CD4
       antibodies, and that gp120-mediated apoptosis is dependent on the period
       of time between the binding of gp120 to CD4 and the encounter with
       antigen. To investigate the different susceptibility to gp120 induced
       apoptosis of primary CD4+ and T cell clones further, the number of
       membrane CD4 molecules and their affinity for gp120, together with Bcl-2
       and Fas expression, were studied. Our data suggest that a
       down-modulation of membrane CD4 together with high expression of the
       Bcl-2 gene and protein characterizes the susceptibility to apoptosis of
       gp120-treated cells. In conclusion, our results define the phenotypic
       features of T cells susceptible to HIV gp120-induced apoptosis and
       demonstrate that the same clonotype, depending on the activation state,
       may present a differential sensitivity to apoptosis induction.
 DE    Animal  Antibodies, Monoclonal/IMMUNOLOGY/PHARMACOLOGY  Antigens,
       CD4/BIOSYNTHESIS/IMMUNOLOGY  Antigens, CD95/BIOSYNTHESIS/GENETICS
       Apoptosis/*DRUG EFFECTS  Base Sequence  Cells, Cultured  CD4-Positive
       T-Lymphocytes/*DRUG EFFECTS/IMMUNOLOGY  Human  HIV Envelope Protein
       gp120/*PHARMACOLOGY  HIV-1/GENETICS/*PHYSIOLOGY  HLA-DR
       Antigens/GENETICS/IMMUNOLOGY  L Cells/DRUG EFFECTS  Lymphocyte
       Transformation  Mice  Molecular Sequence Data  Proto-Oncogene
       Proteins/BIOSYNTHESIS/GENETICS  Recombinant Proteins/IMMUNOLOGY
       Support, Non-U.S. Gov't  Transfection  JOURNAL ARTICLE

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

