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M94A3327.TXT
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1994-10-25
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Document 3327
DOCN M94A3327
TI HIV-infected cells can kill CD4+ cells upon contact.
DT 9412
AU Nardelli B; Gonzalez CJ; Schechter M; Valentine FT; Department of
Medicine, NYU Medical Center, NY 10016.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):101 (abstract no. PA0023). Unique
Identifier : AIDSLINE ICA10/94369248
AB OBJECTIVE: To explore an additional phenomenon by which HIV-1-infected
cells may cause the depletion of CD4+ lymphocytes in vivo. METHODS:
Stimulated PBMC from seronegative donors were infected with HIV-1
clinical isolates. After several days in culture, infected PBMC or CD4+
lymphocytes were incubated with autologous uninfected CD4+ cells that
were prelabeled with 51Chromium. RESULTS: After overnight coculture,
high levels of uninfected target cell lysis, as measured by 51Cr
release, were observed when the infected PBMC were used as effector
cells. Cytotoxicity was not found when uninfected PMBC were used as
effectors. The kinetics of the killing were rapid, since significant
cytolysis occurred after 2 hr. coculture. Moreover, incubation of the
target cells with AZT did not prevent the cell lysis. Syncytia formation
was not observed at any time during the PBMC assays. Binding of gp120 on
the infected cells with the CD4 receptor on the uninfected cells was a
required step, since preincubation of the target cells with soluble
gp120, antibodies against CD4 receptor, or soluble CD4 inhibited the
killing. CD8+ lymphocytes used as target cells were not lysed.
DISCUSSION AND CONCLUSIONS: These results indicate that HIV-infected
cells are capable of killing autologous normal CD4+ cells via a rapid
direct mechanism involving gp120-CD4 interaction but not requiring
productive viral infection of the CD4+ cells. They suggest, therefore,
that a new mechanism of CD4+ cell death might be involved in HIV-1
pathogenicity.
DE Antigens, CD4/METABOLISM Cell Death/DRUG EFFECTS Human HIV Envelope
Protein gp120/METABOLISM HIV
Infections/METABOLISM/*MICROBIOLOGY/PATHOLOGY
HIV-1/PHYSIOLOGY/*PATHOGENICITY In Vitro Leukocytes,
Mononuclear/MICROBIOLOGY Protein Binding T4 Lymphocytes/DRUG
EFFECTS/*MICROBIOLOGY/PATHOLOGY Zidovudine/PHARMACOLOGY MEETING
ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).