International Immunology Advance Access originally published online on June 8, 2005
International Immunology 2005 17(6):769-778; doi:10.1093/intimm/dxh258
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DC-SIGN, but not sDC-SIGN, can modulate IL-2 production from PMA- and anti-CD3-stimulated primary human CD4 T cells
1 Department of Microbiology and Immunology (M/C 790), University of Illinois at Chicago, Room E-709, Building 935, 835 South Wolcott Avenue, Chicago, IL 60612, USA
2 Rush University Medical Center, 1650 West Harrison Street, Chicago, IL 60612, USA
3 Unité de Biologie des Régulations Immunitaires, INSERM E 0352, Institut Pasteur, Paris 75724, France
Correspondence to: B. S. Prabhakar; E-mail: bprabhak{at}uic.edu
Dendritic cell (DC)-specific intercellular cell adhesion molecule-3 (ICAM-3)-grabbing non-integrin (DC-SIGN) is expressed on the surface of DCs and specialized macrophages and can support T cell proliferation. Antibody-mediated co-ligation of CD3 and ICAM-3, the ligand for both DC-SIGN and leukocyte function-associated antigen-1, leads to T cell activation. Therefore, we tested to see whether DC-SIGN or a splice variant of dendritic cell-specific intercellular cell adhesion molecule-3-grabbing non-integrin (sDC-SIGN) can co-stimulate primary human T cells. The sDC-SIGN lacking the transmembrane domain encoded by exon 3 localizes to the cytoplasm of cells and is not secreted. Both B7 and DC-SIGN co-stimulated phorbol myristate acetate-stimulated CD4+ cells as compared with controls. However, unlike B7, both DC-SIGN and sDC-SIGN failed to co-stimulate CD4+ T cells treated with sub-optimal amounts of anti-CD3 (2 µg ml1) as defined by a lack of CD69 and CD25 up-regulation, cell division and cytokine secretion. Instead, DC-SIGN, and not sDC-SIGN, induced a small but consistent down-regulation of IL-2 production by these CD4+ T cells. In contrast, DC-SIGN in the presence of 30 µg ml1 of anti-CD3 modestly up-regulated cytokine production as compared with control. These results suggest that DC-SIGN can differentially modulate T cell stimulation.
Keywords: co-stimulation, dendritic cells, T lymphocytes, tolerance/suppression/anergy
Transmitting editor: C. Terhorst
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