Cross-linking of membrane CD43 mediates dendritic cell maturation.
CD43/leukosialin is a major sialoglycoprotein of the dendritic cell (DC) surface, which can regulate cell adhesion and has the potential to mediate cell activation signals. Monocyte-derived DC transiently incubated with the anti-CD43 mAb, MEM-59, or with F(ab')2 fragments, but not with monovalent Fab fragments or control IgG, 24 h later showed increased levels of membrane HLA-DR, CD54, CD40, CD80, CD86, and CD83. In parallel, CD43 cross-linking induced synthesis and release of IL-1beta, IL-6, TNF-alpha, IL-12, and IL-10. CD43 ligation inhibited the endocytic activity of DC, and enhanced the capacity of DC to stimulate T cell proliferation in the primary allogeneic and autologous MLR assay. In addition, anti-CD43-treated DC were less efficient at presenting native HIV-1 reverse transcriptase to a specific CD4+ T cell clone, whereas presentation of the reverse transcriptase 55-72 peptide to the same clone was increased. Finally, MEM-59 or its F(ab')2 fragments elicited a rise in intracellular free calcium and tyrosine phosphorylation of a 25-kDa protein in DC. The results thus indicate that CD43 cross-linking with specific ligands induces activation and functional maturation of DC.
Corinti
S
S
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
Fanales-Belasio
E
E
Albanesi
C
C
Cavani
A
A
Angelisova
P
P
Girolomoni
G
G
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000954:Antigens, Surface / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis / Q000276:immunology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D051917:Leukosialin; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D010766:Phosphorylation; D012795:Sialoglycoproteins / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D016207:Cytokines; D051917:Leukosialin; D008024:Ligands; D008562:Membrane Glycoproteins; C465014:SPN protein, human; D012795:Sialoglycoproteins; D014443:Tyrosine; D002118:Calcium