Document 3230
 DOCN  M94A3230
 TI    CD4 cross-linking induces aberrant cytokine secretion. Fas antigen
       expression and T-cell apoptosis.
 DT    9412
 AU    Oyaizu N; McCloskey TW; Than S; Hu R; Pahwa S; North Shore University
       Hospital-Cornell University Medical; College, New York.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):123 (abstract no. PA0110). Unique
       Identifier : AIDSLINE ICA10/94369345
 AB    OBJECTIVE: We have recently shown that in unfractioned peripheral blood
       mononuclear cells (PBMC), the crosslinking of CD4 (CD4XL) by itself is
       sufficient to induce T cell apoptosis. The aim of the present study was
       to examine the mechanism of CD4XL-induced T cell apoptosis. We have
       focused on Fas antigen (Fas) expression since Fas might play a critical
       role in T cell apoptosis. METHODS: CD4XL was induced either by anti-CD4
       mAb Leu3a or by HIV-1 envelope protein gp160 in PBMC obtained from
       normal donors. PBMC subpopulations were examined for Fas expression and
       for apoptosis- induction by flow cytometry. Cytokine secretin and
       cytokine mRNA induction were analysed by ELISA and by RT-PCR,
       respectively. RESULTS: We report here two major findings: i) CD4XL was
       found to result in increased Fas Ag expression in lymphocytes and the
       up-regulated Fas was closely correlated with apoptotic cell death, ii)
       CD4XL resulted in induction of INF-gamma and TNF-alpha in the absence of
       IL-2 and IL-4 secretion, and both induced cytokines contributed to Fas
       upregulation. Further, we have observed significantly increased Fas
       expression in T cells from HIV- infected patients compared to normal
       individuals. DISCUSSION AND CONCLUSIONS: These findings strongly suggest
       that aberrant cytokine secretion induced by CD4XL and consequent
       up-regulation of Fas expression might play a critical role in triggering
       T cell apoptosis. Such a mechanism most likely contributes to
       accelerated T cell apoptosis observed in HIV infected individuals.
 DE    Antibodies, Monoclonal/PHARMACOLOGY  Antigens, CD/IMMUNOLOGY/*PHYSIOLOGY
       Antigens, CD4/IMMUNOLOGY/*PHYSIOLOGY  Antigens, Surface/*BIOSYNTHESIS
       *Apoptosis/DRUG EFFECTS  Cells, Cultured  Comparative Study
       Cytokines/*BIOSYNTHESIS  Flow Cytometry  Gene Products,
       env/*PHARMACOLOGY  Human  HIV Infections/*IMMUNOLOGY  HIV-1/*PHYSIOLOGY
       Interferon Type II/BIOSYNTHESIS  Interleukin-2/BIOSYNTHESIS
       Interleukin-4/BIOSYNTHESIS  Protein Precursors/*PHARMACOLOGY
       T-Lymphocytes/CYTOLOGY/DRUG EFFECTS/*IMMUNOLOGY  Tumor Necrosis
       Factor/BIOSYNTHESIS  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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