Identification of RANTES, MIP-1α, and MIP-1β as the major HIV-suppressive factors produced by CD8+ T cells

• Published in: Science (American Association for the Advancement of Science) 1995-12, Vol.270 (5243), p.1811-1815
• Main Authors: COCCHI, F, DEVICO, A. L, GARZINO-DEMO, A, ARYA, S. K, GALLO, R. C, LUSSO, P
• Format: Article
• Language: English
• Subjects: Adult; AIDS/HIV; Amino Acid Sequence; Animals; Antiviral Agents - physiology; Biological and medical sciences; CD8 lymphocytes; CD8-Positive T-Lymphocytes - immunology; Cell Division - physiology; Cell Line; Cells, Cultured; Chemokine CCL4; Chemokine CCL5 - antagonists & inhibitors; Chemokine CCL5 - immunology; Culture Media, Conditioned; Cytokines - antagonists & inhibitors; Cytokines - immunology; Dose-Response Relationship, Immunologic; Escherichia coli; Herpesvirus 6, Human - immunology; Herpesvirus 7, Human - immunology; HIV infection; HIV infections; HIV Infections - immunology; HIV-1 - immunology; HIV-2 - immunology; Human T-lymphotropic virus 1 - immunology; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulin G - immunology; Immunopathology; Lymphocyte Activation; Macaca nemestrina; Macrophage Inflammatory Proteins; Medical sciences; Molecular Sequence Data; Monokines - antagonists & inhibitors; Monokines - immunology; Physiological aspects; Recombinant Proteins - immunology; Simian Immunodeficiency Virus - immunology; T cells
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.270.5243.1811

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.