Moris, A. et al. Dendritic cells and HIV-specific CD4+ T cells: HIV antigen presentation, T cell activation, viral transfer. Blood 108, 1643-1651

Groupe Virus et Immunité, Unité de Recherche Associée (URA) Centre National de la Recherche Scientifique (CNRS) 1930, Paris, France.
Blood (Impact Factor: 10.45). 10/2006; 108(5):1643-51. DOI: 10.1182/blood-2006-02-006361
Source: PubMed


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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Available from: Arnaud Moris, Sep 29, 2015
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    • "HI FBS as previously described [34]. Adult and newborn MoDCs were then washed and 7 Â "
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    Biomaterials 07/2014; 35(31). DOI:10.1016/j.biomaterials.2014.06.043 · 8.56 Impact Factor
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    • "Although DC-SIGN+ cells comprise only 1–5% of total mucosal mononuclear cells, they account for greater than 90% of HIV-1 binding, since DC-SIGN antibodies block 90% of this binding [11]. Previous studies have suggested that DC-SIGN partially contributes to immature DC-mediated HIV-1 transmission and that DC maturation enhances HIV-1 transmission efficiency [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22]. However, the precise mechanisms underlying DC-mediated HIV-1 transmission to CD4+ T cell remain to be defined. "
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    PLoS ONE 03/2012; 7(3):e34521. DOI:10.1371/journal.pone.0034521 · 3.23 Impact Factor
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    • "Thus MR interaction might promote degradation and MHCII Ag presentation in DCs. Capture via DC-SIGN has also been proposed to promote antigen presentation, both in the context of MHCI, following fusion and proteosomal degradation, or MHCII via a pathway independent of productive infection (Moris et al., 2004, 2006). Thus, DC-SIGN, but also other CLRs are involved in uptake of HIV-1 leading to transmission or antigen presentation. "
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    ABSTRACT: Dendritic cells (DCs), Langerhans cells (LCs), and macrophages are innate immune cells that reside in genital and intestinal mucosal tissues susceptible to HIV-1 infection. These innate cells play distinct roles in initiation of HIV-1 infection and induction of anti-viral immunity. DCs are potent migratory cells that capture HIV-1 and transfer virus to CD4(+) T cells in the lymph nodes, whereas LCs have a protective anti-viral function, and macrophages function as viral reservoirs since they produce viruses over prolonged times. These differences are due to the different immune functions of these cells partly dependent on the expression of specific pattern recognition receptors. Expression of Toll-like receptors, C-type lectin receptors, and cell-specific machinery for antigen uptake and processing strongly influence the outcome of virus interactions.
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