Abstract
We investigated the role of blood dendritic cells (DC) in transmission of HIV-1 from infected to uninfected CD4+ T cells, and the accessory molecules involved. DC promoted transmission from infected to uninfected CD4+ cells, but blood DC themselves were not infectable. DC-mediated transmission was blocked by mAb to CD4 and MHC class II, but strongly increased by mAb to CD40 on DC or CD28 on T cells. The DC-dependent infection was inhibitable by anti-CD80 and a soluble fusion protein of the CD80 ligand, CTLA4; soluble CTLA4Ig also blocked infection augmented by crosslinking CD40. We also demonstrated that mAb to CD40 up-regulate the expression of CTLA4 ligands CD80 and B70/B7-2 (CD86) on DC. These data suggest that the dialog between CD40-CD40 ligand (CD40L) and CD28-CD80 counter-receptors on DC and T cells may be linked to HIV infection in vivo.
MeSH terms
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Abatacept
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Antibodies, Blocking / pharmacology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / metabolism
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Antigens, Differentiation / metabolism
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B7-1 Antigen / metabolism
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B7-2 Antigen
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Blood Cells / immunology
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Blood Cells / virology
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CD28 Antigens / metabolism
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / virology*
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CD40 Antigens / metabolism
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CD40 Ligand
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CTLA-4 Antigen
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Cell Communication
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Dendritic Cells / immunology*
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Dendritic Cells / virology*
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HIV Infections / immunology
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HIV Infections / virology
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HIV-1 / pathogenicity*
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HIV-1 / physiology
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Humans
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Immunoconjugates*
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In Vitro Techniques
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Ligands
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Membrane Glycoproteins / metabolism
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Up-Regulation
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Virus Replication
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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CD40 Antigens
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CD86 protein, human
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CTLA-4 Antigen
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CTLA4 protein, human
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Immunoconjugates
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Ligands
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Membrane Glycoproteins
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CD40 Ligand
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Abatacept