The role of CD40 and CD80 accessory cell molecules in dendritic cell-dependent HIV-1 infection.
We investigated the role of blood dendritic cells (DCs) in transmission of HIV-1 from infected to uninfected CD4+ T cells, and the accessory molecules involved. DCs promoted transmission from infected to uninfected CD4+ cells, but DCs 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 DCs 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 CTLA4 immunoglobulin also blocked infection augmented by cross-linking CD40. These data suggest a linkage between CD40-CD40L and CD28-CD80 counterreceptors on DCs and T cells, and spread of HIV infection in vivo.
Pinchuk
L M
LM
Department of Microbiology, University of Washington Medical Center, Seattle 98195.
Polacino
P S
PS
Agy
M B
MB
Klaus
S J
SJ
Clark
E A
EA
D000911:Antibodies, Monoclonal; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D019013:CD40 Antigens; D004279:DNA, Viral / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D015854:Up-Regulation; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D018122:B7-1 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; D004279:DNA, Viral