Oyaizu N, McCloskey TW, Than S, Hu R, Pahwa S; International Conference on AIDS.
Int Conf AIDS. 1994 Aug 7-12; 10: 123 (abstract no. PA0110).
North Shore University Hospital-Cornell University Medical College, New York.
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.
Publication Types:
Keywords:
- Antibodies, Monoclonal
- Antigens, CD4
- Antigens, CD95
- Apoptosis
- Flow Cytometry
- Gene Expression
- HIV Envelope Protein gp160
- HIV Infections
- HIV Seropositivity
- Humans
- Interleukin-2
- T-Lymphocytes
- TNF protein, human
- Tumor Necrosis Factor-alpha
- Up-Regulation
- genetics
- immunology
Other ID:
UI: 102208171
From Meeting Abstracts