Document Type
Article
Publication Date
2005
Keywords
CD4 antigen, interleukin 4, dendritic cell, gene expression, HIV-1, lymph node, macrophage, T lymphocyte
Abstract
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.
Recommended Citation
Granelli-Piperno, A., A. Pritsker, M. Pack, I. Shimeliovich, J. -F Arrighi, C. G. Park, C. Trumpfheller, V. Piguet, T. M. Moran, and R. M. Steinman. 2005. "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." Journal of Immunology 175 (7): 4265-4273
Comments
Open Access