title: Peripheral blood mononuclear cells of HIV-infected patients contain CD8 T cells that form conjugates with and kill HIV-infected autologous CD4 T cells.
abstract: Peripheral blood mononuclear cells (PBMC) of untreated, HIV-infected patients contain HIV-specific CD8 T cells as well as their corresponding targets, HIV-infected CD4 T cells. To determine if CD4 T-cell depletion in HIV-infected patients may result from autologous CD8-CD4 T-cell interaction, CD8 and CD4 T cells procured from PBMC of acute and chronic untreated HIV-infected patients were sorted and co-incubated. Formation of CD8-CD4 T-cell conjugates was observed by fluorescence microscopy. Apoptosis of CD4 T cells in conjugation was recorded by digitized images and was further observed and measured by FACS using Annexin staining. Perforin expression in the CD8 T cells was measured using intracellular monoclonal perforin antibody staining. HIV DNA in the conjugated CD4 T cells was detected by in situ PCR. We found that 6·1 ± 0·5% of CD4 T cells from acute HIV-infected patients and 3·0 ± 0·5% from chronic HIV-infected patients formed CD8-CD4 T-cell conjugates. Annexin binding and cell morphology typical of apoptosis were observed in the conjugated CD4 T cells. The majority of CD8 T cells that had conjugated to CD4 T cells expressed perforin. The conjugated CD4 T cells exhibited nuclear HIV DNA. CD8 T cells and HIV-infected CD4 T cells, both procured from the PBMC of untreated HIV-infected patients, form conjugates. Apoptotic lytic activity has been observed in the conjugated CD4 T cells. We propose that CD4 T-cell annihilation in HIV-infected patients results, at least in part, from the interactions of perforin-rich CD8 T cells with autologous, HIV-infected CD4 T cells.
authors.affiliation: Department of Internal Medicine 'H' and the Kobler AIDS Centre, Tel-Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Chorin
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Gal-Garber
authors.affiliation: Department of Internal Medicine 'H' and the Kobler AIDS Centre, Tel-Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Yagel
authors.affiliation: Department of Internal Medicine 'H' and the Kobler AIDS Centre, Tel-Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Turner
authors.affiliation: Department of Internal Medicine 'H' and the Kobler AIDS Centre, Tel-Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Avidor
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Gideon
authors.initials: G
authors.lastname: Berke
authors.affiliation: Department of Internal Medicine 'H' and the Kobler AIDS Centre, Tel-Aviv Sourasky Medical Centre, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Hassin
keywords: 
  HIV
  ; CD4 T cells; CD8 T cells; apoptosis