CC chemokines produced by CD8+ T cells are known to act as HIV-suppressive factors. We studied the possible role of these chemokines in HIV-1–specific killing of target cells. We found that the activity of cytotoxic T lymphocytes (CTLs) in CTL lines or freshly isolated peripheral blood mononuclear cells from HIV-1–infected individuals is markedly enhanced by RANTES (regulated on activation, normal T cell expressed and secreted) and virtually abolished by an antibody neutralizing RANTES or the RANTES receptor antagonist RANTES(9-68). Lysis was mediated by CD8+ major histocompatibility complex class I–restricted T cells and was obtained with target cells expressing epitopes of the HIV-1LAI proteins Gag, Pol, Env, and Nef. The cytolytic activity observed in the presence or absence of added RANTES could be abolished by pretreatment of the CTLs with pertussis toxin, indicating that the effect is mediated by a G protein–coupled receptor. The chemokines monocyte chemotactic protein (MCP)-3, MCP-4, and eotaxin acted like RANTES, whereas macrophage inflammatory protein (MIP)-1α, MIP-1β, MCP-1, and stromal cell–derived factor 1 were inactive, suggesting a role for the eotaxin receptor, CCR3, and ruling out the involvement of CCR1, CCR2, CCR5, and CXCR4. CTL activity was abrogated by an antibody that blocks CCR3, further indicating that specific lysis is triggered via this chemokine receptor. These observations reveal a novel mechanism for the induction of HIV-1–specific cytotoxicity that depends on RANTES acting via CCR3.
Skip Nav Destination
Article navigation
3 August 1998
Brief Definitive Report|
August 03 1998
HIV-specific T Cell Cytotoxicity Mediated by RANTES Via the Chemokine Receptor CCR3
Fabienne Hadida,
Fabienne Hadida
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Search for other works by this author on:
Vincent Vieillard,
Vincent Vieillard
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Search for other works by this author on:
Brigitte Autran,
Brigitte Autran
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Search for other works by this author on:
Ian Clark-Lewis,
Ian Clark-Lewis
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Search for other works by this author on:
Marco Baggiolini,
Marco Baggiolini
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Search for other works by this author on:
Patrice Debré
Patrice Debré
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Search for other works by this author on:
Fabienne Hadida
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Vincent Vieillard
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Brigitte Autran
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Ian Clark-Lewis
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Marco Baggiolini
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Patrice Debré
From the *Laboratoire d'Immunologie Cellulaire, Unité de Recherche Associée, Centre National de la Recherche Scientifique 625, Bâtiment Centre d'Études et de Recherches en Virologie et Immunologie, Hôpital Pitié-Salpétrière, 75013 Paris, France; ‡UMR 146 Centre National de la Recherche Scientifique, Institut Curie, 91405 Orsay, France; the §Biomedical Research Centre, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada; and the ‖Theodor Kocher Institute, University of Bern, CH-3000 Bern 9, Switzerland
Address correspondence to Patrice Debré, Laboratoire d'Immunologie Cellulaire, Bâtiment CERVI, Hôpital Pitié-Salpétrière, Boulevard de l'Hopital 83, 75013 Paris, France. Phone: 33-1-4217-7482; Fax: 33-1-4217-7490; E-mail: [email protected]
We are particularly indebted to Dr. Fernando Arenzana (Institut Pasteur, Paris) and Beatrice Dewald (Theodor Kocher Institute, Bern) for discussions and important suggestions.
Received:
April 29 1998
Revision Received:
May 29 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 188 (3): 609–614.
Article history
Received:
April 29 1998
Revision Received:
May 29 1998
Citation
Fabienne Hadida, Vincent Vieillard, Brigitte Autran, Ian Clark-Lewis, Marco Baggiolini, Patrice Debré; HIV-specific T Cell Cytotoxicity Mediated by RANTES Via the Chemokine Receptor CCR3 . J Exp Med 3 August 1998; 188 (3): 609–614. doi: https://doi.org/10.1084/jem.188.3.609
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionEmail alerts
Advertisement
