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 Blood, 1 September 2006, Vol. 108, No. 5, pp. 1643-1651.
Prepublished online as a Blood First Edition Paper on May 4, 2006; DOI 10.1182/blood-2006-02-006361.

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IMMUNOBIOLOGY

Dendritic cells and HIV-specific CD4+ T cells: HIV antigen presentation, T-cell activation, and viral transfer

Arnaud Moris, Anthony Pajot, Fabien Blanchet, Florence Guivel-Benhassine, Margarita Salcedo, and Olivier Schwartz

From the Groupe Virus et Immunité, Unité de Recherche Associée (URA) Centre National de la Recherche Scientifique (CNRS) 1930, Paris; Unité d'Immunité Cellulaire Antivirale, Institut Pasteur, Paris; and IDM Research Laboratories, Institut des Cordeliers, Paris, France.

Human immunodeficiency virus (HIV)-specific CD4+ lymphocytes are preferentially infected in HIV-positive individuals. To study this preferential infection, we have derived several HIV-specific (HS) CD4+ clones. We show that in dendritic cells (DCs), HIV virion capture led to major histocompatibility complex class-II (MHC-II)-restricted viral antigen presentation and to activation of HS cells. In contrast, neither cell-free virions nor infected lymphocytes activated HS cells. In DCs, the dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN/CD209), which internalizes virions, promoted MHC-II presentation of HIV antigens. Activation of HS cells by HIV-exposed DCs triggered an efficient viral spread in lymphocytes. CD4+ clones with irrelevant antigenic specificities were not activated by HIV-exposed DCs and poorly supported viral replication under this setting. Our results unravel the mechanisms of MHC-II-restricted HIV antigen presentation by DCs and describe how HIV gains access to the very cells designed by the immune system to counteract this pathogen.


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