DC-SIGN, but not sDC-SIGN, can modulate IL-2 production from PMA- and anti-CD3-stimulated primary human CD4 T cells.
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 microg 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 mug 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.
Martinez
Osvaldo
O
Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612, USA.
Brackenridge
Scott
S
El-Idrissi
Mohammed El-Azami
Mel-A
Prabhakar
Bellur S
BS
D017398:Alternative Splicing; D000818:Animals; D000906:Antibodies; D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D017930:Genes, Reporter; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000906:Antibodies; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D020033:Protein Isoforms; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin