Abstract
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.
MeSH terms
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Adult
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Amino Acid Sequence
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Animals
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Antiviral Agents / physiology*
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CD8-Positive T-Lymphocytes / immunology*
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Cell Division / physiology
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Cell Line
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Cells, Cultured
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Chemokine CCL4
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Chemokine CCL5 / antagonists & inhibitors
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Chemokine CCL5 / immunology*
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Culture Media, Conditioned
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Cytokines / antagonists & inhibitors
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Cytokines / immunology*
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Dose-Response Relationship, Immunologic
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Escherichia coli
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HIV Infections / immunology
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HIV-1 / immunology*
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HIV-2 / immunology
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Herpesvirus 6, Human / immunology
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Herpesvirus 7, Human / immunology
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Human T-lymphotropic virus 1 / immunology
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Humans
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Immunoglobulin G / immunology
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Lymphocyte Activation
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Macaca nemestrina
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Macrophage Inflammatory Proteins
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Molecular Sequence Data
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Monokines / antagonists & inhibitors
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Monokines / immunology*
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Recombinant Proteins / immunology
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Simian Immunodeficiency Virus / immunology
Substances
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Antiviral Agents
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Chemokine CCL4
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Chemokine CCL5
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Culture Media, Conditioned
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Cytokines
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Immunoglobulin G
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Macrophage Inflammatory Proteins
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Monokines
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Recombinant Proteins