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).