title: Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4.
abstract: CD8-positive T cells are thought to play an important role in the control of infection by human immunodeficiency virus (HIV) as a result of their cytotoxic activity and by releasing soluble factors. In AIDS patients, the absolute number of CD8+ T lymphocytes is decreased in peripheral blood and their turnover rate is increased, suggesting that there is more cell renewal and cell death occurring. Anti-retroviral therapy raises CD8+ T-cell counts in HIV-infected patients. Here we report that the death rate of CD8+ T cells by apoptosis increased markedly during HIV infection of peripheral blood mononuclear cells in vitro. Apoptosis is induced in a dose-dependent manner by recombinant envelope glycoprotein gp120 from HIV strain X4, or by stromal-derived factor-1 (SDF-1), the physiological ligand of the chemokine receptor CXCR4. Apoptosis is mediated by the interaction between tumour-necrosis factor-alpha bound to the membrane of macrophages (mbTNF) and a receptor on CD8+ T cells (TNF-receptor II, or TNFRII). The expression of both of these cell-surface proteins is upregulated by HIV infection or by treatment with recombinant gp120 or SDF-1. Apoptosis of CD8+ T cells isolated from HIV-infected patients is also mediated by macrophages through the interaction between mbTNF and TNFRII. These results indicate that the increased turnover of CD8+ T cells in HIV-infected subjects is mediated by the HIV envelope protein through the CXCR4 chemokine receptor.
authors.affiliation: The Picower Institute for Medical Research, Manhasset, New York 11010, USA.
authors.forename: G
authors.initials: G
authors.lastname: Herbein
authors.forename: U
authors.initials: U
authors.lastname: Mahlknecht
authors.forename: F
authors.initials: F
authors.lastname: Batliwalla
authors.forename: P
authors.initials: P
authors.lastname: Gregersen
authors.forename: T
authors.initials: T
authors.lastname: Pappas
authors.forename: J
authors.initials: J
authors.lastname: Butler
authors.forename: W A
authors.initials: WA
authors.lastname: O'Brien
authors.forename: E
authors.initials: E
authors.lastname: Verdin
mesh_terms: D000954:Antigens, Surface / Q000502:physiology; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D002450:Cell Communication; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008264:Macrophages / Q000502:physiology* / Q000821:virology; D019718:Receptors, CXCR4 / Q000502:physiology; D018523:Tropism
chemical_list: D000954:Antigens, Surface; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4