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Science 15 December 1995:
Vol. 270. no. 5243, pp. 1811 - 1815
DOI: 10.1126/science.270.5243.1811
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Reports

Identification of RANTES, MIP-1, and MIP-1 as the Major HIV-Suppressive Factors Produced by CD8+ T Cells

Fiorenza Cocchi (1),  Anthony L. DeVico,  Alfredo Garzino-Demo,  Suresh K. Arya,  Robert C. Gallo (1) (2),  Paolo Lusso (3)

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-1alpha, and MIP-1beta 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-1alpha. RANTES, MIP-1alpha, and MIP-1beta 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-1alpha, and MIP-1beta. Recombinant human RANTES, MIP-1alpha, and MIP-1beta 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.


F. Cocchi, A. Garzino-Demo, S. K. Arya, R. C. Gallo, P. Lusso, Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20892, USA.
A. L. DeVico, Advanced BioScience Laboratories, Kensington, MD 20852, USA.
(1) Present address: Institute of Human Virology, Medical Biotechnology Center, University of Maryland Biotechnology Institute (UMBI), University of Maryland, Baltimore, MD 21201, USA.
(2) To whom correspondence and reprint requests should be addressed at Institute of Human Virology, Suite 200, Medical Biotechnology Center, UMBI, University of Maryland, Baltimore, MD 21201, USA.
(3) Present address: Unit of Human Virology, DIBIT, San Raffaele Scientific Institute, 20132 Milano, Italy, and Institute of Human Virology, Baltimore, MD 21201, USA.


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J. Immunol. 174, 5655-5664
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Differential effects of R5 and X4 human immunodeficiency virus type 1 infection on CD4+ cell proliferation and activation.
C. P. Locher, S. A. Witt, R. Kassel, N. L. Dowell, S. Fujimura, and J. A. Levy (2005)
J. Gen. Virol. 86, 1171-1179
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Preferential Use of CXCR4 by R5X4 Human Immunodeficiency Virus Type 1 Isolates for Infection of Primary Lymphocytes.
Y. Yi, F. Shaheen, and R. G. Collman (2005)
J. Virol. 79, 1480-1486
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Agonist-induced Endocytosis of CC Chemokine Receptor 5 Is Clathrin Dependent.
N. Signoret, L. Hewlett, S. Wavre, A. Pelchen-Matthews, M. Oppermann, and M. Marsh (2005)
Mol. Biol. Cell 16, 902-917
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CD8+ T-Cell-Mediated Cross-Clade Protection in the Genital Tract following Intranasal Immunization with Inactivated Human Immunodeficiency Virus Antigen Plus CpG Oligodeoxynucleotides.
J. Q. Jiang, A. Patrick, R. B. Moss, and K. L. Rosenthal (2005)
J. Virol. 79, 393-400
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Structural Determinants of the Anti-HIV Activity of a CCR5 Antagonist Derived from Toxoplasma gondii.
F. Yarovinsky, J. F. Andersen, L. R. King, P. Caspar, J. Aliberti, H. Golding, and A. Sher (2004)
J. Biol. Chem. 279, 53635-53642
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Inhibition of Human Immunodeficiency Virus Replication by a Dual CCR5/CXCR4 Antagonist.
K. Princen, S. Hatse, K. Vermeire, S. Aquaro, E. De Clercq, L.-O. Gerlach, M. Rosenkilde, T. W. Schwartz, R. Skerlj, G. Bridger, et al. (2004)
J. Virol. 78, 12996-13006
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Medicinal chemistry applied to a synthetic protein: Development of highly potent HIV entry inhibitors.
O. Hartley, H. Gaertner, J. Wilken, D. Thompson, R. Fish, A. Ramos, C. Pastore, B. Dufour, F. Cerini, A. Melotti, et al. (2004)
PNAS 101, 16460-16465
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Involvement of Fc{gamma}R I (CD64) in the Mechanism of HIV-1 Inhibition by Polyclonal IgG Purified from Infected Patients in Cultured Monocyte-Derived Macrophages.
V. Holl, S. Hemmerter, R. Burrer, S. Schmidt, A. Bohbot, A.-M. Aubertin, and C. Moog (2004)
J. Immunol. 173, 6274-6283
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Platelet Microbicidal Protein 1: Structural Themes of a Multifunctional Antimicrobial Peptide.
N. Y. Yount, K. D. Gank, Y. Q. Xiong, A. S. Bayer, T. Pender, W. H. Welch, and M. R. Yeaman (2004)
Antimicrob. Agents Chemother. 48, 4395-4404
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Recall antigen activation induces prompt release of CCR5 ligands from PBMC: implication in memory responses and immunization.
L. Sun, S. F. Abdelwahab, G. K. Lewis, and A. Garzino-Demo (2004)
Int. Immunol. 16, 1623-1631
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Mannose-Specific Plant Lectins from the Amaryllidaceae Family Qualify as Efficient Microbicides for Prevention of Human Immunodeficiency Virus Infection.
J. Balzarini, S. Hatse, K. Vermeire, K. Princen, S. Aquaro, C.-F. Perno, E. De Clercq, H. Egberink, G. Vanden Mooter, W. Peumans, et al. (2004)
Antimicrob. Agents Chemother. 48, 3858-3870
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Profile of Resistance of Human Immunodeficiency Virus to Mannose-Specific Plant Lectins.
J. Balzarini, K. Van Laethem, S. Hatse, K. Vermeire, E. De Clercq, W. Peumans, E. Van Damme, A.-M. Vandamme, A. Bohlmstedt, and D. Schols (2004)
J. Virol. 78, 10617-10627
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Inhibition of human immunodeficiency virus type 1 replication by Z-100, an immunomodulator extracted from human-type tubercle bacilli, in macrophages.
Y. Emori, T. Ikeda, T. Ohashi, T. Masuda, T. Kurimoto, M. Takei, and M. Kannagi (2004)
J. Gen. Virol. 85, 2603-2613
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Beyond Help: Direct Effector Functions of Human Immunodeficiency Virus Type 1-Specific CD4+ T Cells.
P. J. Norris, H. F. Moffett, O. O. Yang, D. E. Kaufmann, M. J. Clark, M. M. Addo, and E. S. Rosenberg (2004)
J. Virol. 78, 8844-8851
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Nef Stimulates Human Immunodeficiency Virus Type 1 Replication in Primary T Cells by Enhancing Virion-Associated gp120 Levels: Coreceptor-Dependent Requirement for Nef in Viral Replication.
C. A. Lundquist, J. Zhou, and C. Aiken (2004)
J. Virol. 78, 6287-6296
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High Beta-Chemokine Expression Levels in Lymphoid Tissues of Simian/Human Immunodeficiency Virus 89.6-Vaccinated Rhesus Macaques Are Associated with Uncontrolled Replication of Simian Immunodeficiency Virus Challenge Inoculum.
L. LaFranco-Scheuch, K. Abel, N. Makori, K. Rothaeusler, and C. J. Miller (2004)
J. Virol. 78, 6399-6408
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Induction of HIV Immunity in the Genital Tract After Intranasal Delivery of a MVA Vector: Enhanced Immunogenicity After DNA Prime-Modified Vaccinia Virus Ankara Boost Immunization Schedule.
M. M. Gherardi, E. Perez-Jimenez, J. L. Najera, and M. Esteban (2004)
J. Immunol. 172, 6209-6220
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Mycobacterium tuberculosis-Induced CXCR4 and Chemokine Expression Leads to Preferential X4 HIV-1 Replication in Human Macrophages.
Y. Hoshino, D. B. Tse, G. Rochford, S. Prabhakar, S. Hoshino, N. Chitkara, K. Kuwabara, E. Ching, B. Raju, J. A. Gold, et al. (2004)
J. Immunol. 172, 6251-6258
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Phenotypic and Genotypic Comparisons of CCR5- and CXCR4-Tropic Human Immunodeficiency Virus Type 1 Biological Clones Isolated from Subtype C-Infected Individuals.
G. Pollakis, A. Abebe, A. Kliphuis, M. I. M. Chalaby, M. Bakker, Y. Mengistu, M. Brouwer, J. Goudsmit, H. Schuitemaker, and W. A. Paxton (2004)
J. Virol. 78, 2841-2852
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Early protection against pathogenic virus infection at a mucosal challenge site after vaccination with attenuated simian immunodeficiency virus.
K. Tenner-Racz, C. S. Hennig, K. Uberla, H. Stoiber, R. Ignatius, J. Heeney, R. M. Steinman, and P. Racz (2004)
PNAS 101, 3017-3022
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TNF Receptor Signaling Contributes to Chemokine Secretion, Inflammation, and Respiratory Deficits during Pneumocystis Pneumonia.
T. W. Wright, G. S. Pryhuber, P. R. Chess, Z. Wang, R. H. Notter, and F. Gigliotti (2004)
J. Immunol. 172, 2511-2521
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Chemokine Receptor 5 Is Dispensable for Innate and Adaptive Immune Responses to Listeria monocytogenes Infection.
M. X. Zhong, W. A. Kuziel, E. G. Pamer, and N. V. Serbina (2004)
Infect. Immun. 72, 1057-1064
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Intrapatient Alterations in the Human Immunodeficiency Virus Type 1 gp120 V1V2 and V3 Regions Differentially Modulate Coreceptor Usage, Virus Inhibition by CC/CXC Chemokines, Soluble CD4, and the b12 and 2G12 Monoclonal Antibodies.
A. A. Nabatov, G. Pollakis, T. Linnemann, A. Kliphius, M. I. M. Chalaby, and W. A. Paxton (2004)
J. Virol. 78, 524-530
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