Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4

• Published in: Nature (London) Vol. 395; no. 6698; pp. 189 - 194
• Main Authors: Herbein, Georges, Mahlknecht, Ulrich, Batliwalla, Franak, Gregersen, Peter, Pappas, Todd, Butler, John, O'Brien, William A., Verdin, Eric
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.09.1998; Nature Publishing; Nature Publishing Group
• Subjects: Antigens, Surface - physiology; Apoptosis; Biological and medical sciences; CD8-Positive T-Lymphocytes - pathology; Cell Communication; Cells, Cultured; Cellular biology; Chemokine CXCL12; Chemokines, CXC - physiology; Fundamental and applied biological sciences. Psychology; HIV; HIV Envelope Protein gp120 - physiology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - pathogenicity; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Immune system; letter; Leukocytes; Leukocytes, Mononuclear - virology; Lymphocytes; Macrophages - physiology; Macrophages - virology; Microbiology; multidisciplinary; Proteins; Receptors, CXCR4 - physiology; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Science; Science (multidisciplinary); Tropism; Virology; Virus; T-Lymphocyte; Retroviridae; Cytotoxicity; Human immunodeficiency virus; Lentivirus; Virus envelope; Host virus relation; Apoptosis; Macrophage
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/26026

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 1 , 2 . In AIDS patients, the absolute number of CD8 + T lymphocytes is decreased in peripheral blood 3 , 4 and their turnover rate is increased, suggesting that there is more cell renewal and cell death occurring 5 . Anti-retroviral therapy raises CD8 + T-cell counts in HIV-infected patients 6 , 7 , 8 . 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-α 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.