Antibodies against sialophorin (CD43) enhance the capacity of dendritic cells to cluster and activate T lymphocytes.
CD43 is a leukocyte membrane glycoprotein rich in negatively charged sialic acid residues that may act as an anti-adhesion molecule. In this study, we analyzed the expression and function of CD43 on epidermal Langerhans cells (LC) and dendritic cells derived from adherent peripheral blood monocytes treated with granulocyte-macrophage CSF and IL-4 (Mo-DC). Both freshly isolated LC (fLC) and Mo-DC expressed uniformly high amounts of membrane CD43, with levels unchanged in 48-h cultured LC or in TNF-alpha-treated Mo-DC. When fLC or Mo-DC were transiently preincubated with anti-CD43 mAb or neuraminidase, they formed much larger clusters with T cells as compared with cells incubated with control mAb. Moreover, a significantly increased proliferation of naive allogeneic T cells in a primary MLR assay was induced. Anti-CD43-treated Mo-DC also presented tetanus toxoid to primed T cells more efficiently. Immunofluorescence and immunogold electron microscopy showed that following Ab cross-linking and warming to 37 degrees C, CD43 is progressively removed from the cell surface and is internalized within endosomes and vacuoles. In addition, fLC and Mo-DC incubated with anti-CD43 mAb increased expression of HLA-DR, ICAM-1, B7-1, B7-2, CD40, and CD83 after 24 h, and this was partially prevented by culturing cells in the presence of cycloheximide. We thus postulate that membrane CD43, other than serving as anti-adhesion molecule, can mediate activation signals in immature DC, leading to augmented expression of adhesion/costimulatory molecules and Ag-presenting function.
Fanales-Belasio
E
E
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
Zambruno
G
G
Cavani
A
A
Girolomoni
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D017951:Antigen Presentation / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004705:Endocytosis; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007801:Langerhans Cells / Q000187:drug effects* / Q000276:immunology; D051917:Leukosialin; D008213:Lymphocyte Activation / Q000502:physiology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D009439:Neuraminidase / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000276:immunology* / Q000502:physiology; D000097802:CD83 Antigen
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D003513:Cycloheximide; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D018799:Intercellular Adhesion Molecule-1; D051917:Leukosialin; D008562:Membrane Glycoproteins; D009439:Neuraminidase; D011500:Protein Synthesis Inhibitors; D012795:Sialoglycoproteins; D000097802:CD83 Antigen; C497964:CD86 protein, human; C465014:SPN protein, human