title: HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative γδ T cells which are lost during progression to AIDS.
abstract: HIV infects and replicates in CD4+ T cells but effects on host immunity and disease also involve depletion, hyper-activation, and modification of CD4-negative cell populations. In particular, the depletion of CD4-negative γδ T cells is common to all HIV+ individuals. We found that soluble or cell-associated envelope glycoproteins from CCR5-tropic strains of HIV could bind, activates the p38-caspase pathway, and induce the death of γδ cells. Envelope binding requires integrin α4β7 and chemokine receptor CCR5 which are at high levels and form a complex on the γδ T cell membrane. This receptor complex facilitated V3 loop binding to CCR5 in the absence of CD4-induced conformational changes. Cell death was increased by antigen stimulation after exposure to envelope glycoprotein. Direct signaling by envelope glycoprotein killed CD4-negative γδ T cells and reproduced a defect observed in all patients with HIV disease.
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Haishan
authors.initials: H
authors.lastname: Li
authors.forename: C David
authors.initials: CD
authors.lastname: Pauza
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D018450:Disease Progression; D006678:HIV / Q000235:genetics / Q000502:physiology / Q000648:ultrastructure; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology / Q000502:physiology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D016023:Integrins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019713:Receptors, CCR5; D014759:Viral Envelope Proteins; C071777:integrin alpha4beta7