Cell-cell interactions regulate dendritic cell-dependent HIV-1 production in CD4+ T lymphocytes.
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.
Regional Primate Research Center, University of Washington Medical Center, Seattle 98195, USA.
L M
LM
Pinchuk
P S
PS
Polacino
M B
MB
Agy
S J
SJ
Klaus
E A
EA
Clark
D000069594:Abatacept; D019138:Antibodies, Blocking / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D001773:Blood Cells / Q000276:immunology / Q000821:virology; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D060908:CTLA-4 Antigen; D002450:Cell Communication; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D018796:Immunoconjugates; D066298:In Vitro Techniques; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D015854:Up-Regulation; D014779:Virus Replication
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D000069594:Abatacept