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M94A3230.TXT
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1994-10-25
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45 lines
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
protected by Copyright Law (Title 17, U.S.Code).