DC-SIGN, but not sDC-SIGN, can modulate IL-2 production from PMA- and anti-CD3-stimulated primary human CD4 T cells

• Published in: International immunology 2005-06, Vol.17 (6), p.769-778
• Main Authors: Martinez, Osvaldo, Brackenridge, Scott, El-Idrissi, Mohammed El-Azami, Prabhakar, Bellur S.
• Format: Article
• Language: English
• Subjects: 6-diamidino-2-phenylindole; Alternative Splicing; Animals; Antibodies; Antigens, CD - analysis; APC antigen-presenting cell; CD4-Positive T-Lymphocytes - immunology; Cell Adhesion Molecules - biosynthesis; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - immunology; Cells, Cultured; CFSE 5-(and-6)-carboxyfluorescein diacetate; CHO Cells - metabolism; Cloning, Molecular; co-stimulation; Cricetinae; Cricetulus; DAPI 4; DC-SIGN dendritic cell-specific intercellular cell adhesion molecule-3-grabbing non-integrin; DC dendritic cell; dendritic cells; FSC forward scatter; Genes, Reporter; GM-CSF granulocyte macrophage colony- stimulating factor; Humans; ICAM intercellular cell adhesion molecule; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Lectins, C-Type - biosynthesis; Lectins, C-Type - genetics; Lectins, C-Type - immunology; LFA leukocyte function-associated antigen; Lymphocyte Activation; Lymphocyte Subsets - immunology; PMA phorbol myristate acetate; Protein Isoforms - biosynthesis; Protein Isoforms - genetics; Protein Isoforms - immunology; Receptors, Cell Surface - biosynthesis; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Reverse Transcriptase Polymerase Chain Reaction; sDC-SIGN a splice variant of dendritic cell-specific intercellular cell adhesion molecule-3-grabbing non-integrin; succinimidyl ester; T lymphocytes; TMB tetramethylbenzidine; tolerance/suppression/anergy; Transfection
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxh258

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 ml−1) 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 ml−1 of anti-CD3 modestly up-regulated cytokine production as compared with control. These results suggest that DC-SIGN can differentially modulate T cell stimulation.