Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction.
The C-type lectin dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN)/CD209 efficiently binds several pathogens, including HIV-1. DC-SIGN is expressed on monocyte-derived DCs in culture, and importantly, it is able to sequester HIV-1 within cells and facilitate transmission of virus to CD4+ T cells. To investigate DC-SIGN function, we have generated new mAbs. We report in this study that these and prior anti-DC-SIGN mAbs primarily label macrophages in the medullary sinuses of noninflamed human lymph node. In contrast, expression is not detected on most DCs in the T cell area, except for occasional cells. We also noted that IL-4 alone can induce expression of DC-SIGN in CD14+ monocytes and circulating blood DCs. However, blockade of DC-SIGN with Abs and DC-SIGN small interfering RNA did not result in a major reduction in the capacity of these DCs to transfer HIV to T cells, confirming significant DC-SIGN-independent mechanisms. The blocking approaches did reduce HIV-1 transmission by DC-SIGN-transfected cells by >90%. DC-SIGN blockade also did not reduce the ability of DCs to stimulate T cell proliferation in the MLR. These results indicate that DC-SIGN has the potential to contribute to macrophage function in normal human lymph node, and that DCs do not require DC-SIGN to transmit HIV or to initiate T cell responses.
Granelli-Piperno
Angela
A
Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, Rockefeller University, New York, NY 10021, USA.
Pritsker
Alla
A
Pack
Maggi
M
Shimeliovich
Irina
I
Arrighi
Jean-Francois
JF
Park
Chae Gyu
CG
Trumpfheller
Christine
C
Piguet
Vincent
V
Moran
Thomas M
TM
Steinman
Ralph M
RM
D000818:Animals; D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D004285:Dogs; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology; D014162:Transfection; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin