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The Journal of Immunology, 1998, 161: 4257-4267.
Copyright © 1998 by The American Association of Immunologists

Chronically HIV-1-Infected Monocytic Cells Induce Apoptosis in Cocultured T Cells¹

Houchu Chen^*, Y. K. Yip, Italas George^*, Max Tyorkin^*, Erez Salik^* and Kirk Sperber^2,*

^* Division of Clinical Immunology, Mount Sinai Medical Center, and Department of Biological Sciences, Hunter College, City University of New York, New York, NY 10029

We have previously developed a human macrophage hybridoma model system to study the effect of HIV-1 infection on monocytic function. Upon coculture of one chronically (35 days postinfection) HIV-1-infected human macrophage hybridoma cell line, 43_HIV, there was a dose-dependent decrease in the viability of cocultured Ag-stimulated T cells associated with an increase in DNA strand breaks. Enhanced apoptosis was determined by labeling with biotinylated dUTP and propidium iodide, increased staining with annexin V, increased side light scatter and expression of CD95, and decreased forward light scatter and expression of Bcl-2. There was also increased DNA strand breaks as determined by propidium iodide staining in unstimulated T cells cocultured with 43_HIV and in T cells stimulated with anti-CD3 mAb and PHA. Pretreatment with 5145, a human polyclonal anti-gp120 Ab that recognizes the CD4 binding region, as well as with an anti-Fas ligand mAb blocked apoptosis in CD4⁺ T cells but not in CD8⁺ T cells. A soluble factor with a M_r below 10,000 Da was defined that induced apoptosis in CD4⁺ and CD8⁺ T cells and B cells. SDS-PAGE analysis of the active fractions revealed a band of 6000 Da that, after electroelution, had proapoptotic activity. The pI of the activity was estimated to be between 6.5 and 7.0. In conclusion, chronically HIV-1-infected monocytic cells induce apoptosis in bystander-, Ag-, anti-CD3-, and mitogen-stimulated T cells by multiple factors, which may contribute to the depletion of lymphocytes induced by HIV-1.

Related articles in The JI:

Chronically HIV-1-infected monocytic cells induce apoptosis in cocultured T cells.

H. Chen, Y. K. Yip, I. George, M. Tyorkin, E. Salik, and K. Sperber
The JI 2005 175: 8443-8444. [Full Text]  

Retraction: Chronically HIV-1-Infected Monocytic Cells Induce Apoptosis in Cocultured T Cells

Houchu Chen, Italas George, Max Tyorkin, Erez Salik, and Kirk Sperber
The JI 2006 177: 6560. [Full Text]  

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