Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells.
Evidence suggests that CD8+ T lymphocytes are involved in the control of human immunodeficiency virus (HIV) infection in vivo, either by cytolytic mechanisms or by the release of HIV-suppressive factors (HIV-SF). The chemokines RANTES, MIP-1 alpha, and MIP-1 beta were identified as the major HIV-SF produced by CD8+ T cells. Two active proteins purified from the culture supernatant of an immortalized CD8+ T cell clone revealed sequence identity with human RANTES and MIP-1 alpha. RANTES, MIP-1 alpha, and MIP-1 beta were released by both immortalized and primary CD8+ T cells. HIV-SF activity produced by these cells was completely blocked by a combination of neutralizing antibodies against RANTES, MIP-1 alpha, and MIP-1 beta. Recombinant human RANTES, MIP-1 alpha, and MIP-1 beta induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). These data may have relevance for the prevention and therapy of AIDS.
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA.
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D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000276:immunology*; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D015498:HIV-2 / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology; D016199:Herpesvirus 7, Human / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008213:Lymphocyte Activation; D008254:Macaca nemestrina; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D015846:Monokines / Q000037:antagonists & inhibitors / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology
D000998:Antiviral Agents; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D017077:Culture Media, Conditioned; D016207:Cytokines; D007074:Immunoglobulin G; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins