Cross-linking of membrane CD43 mediates dendritic cell maturation

CD43/leukosialin is a major sialoglycoprotein of the dendritic cell (DC) su rface, which can regulate cell adhesion and has the potential to mediate ce ll activation signals. Monocyte-derived DC transiently incubated with the a nti-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 membran e HLA-DR, CD54, CD40, CD80, CD86, and CD83, In parallel, CD43 cross-linking induced synthesis and release of IL-1 beta, 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 effi cient at presenting native HIV-1 reverse transcriptase to a specific CD4(+) T cell clone, whereas presentation;of the reverse transcriptase 55-72 pept ide to the same clone was increased, Finally, MEM-59 or its F(ab')(2) fragm ents elicited a rise in intracellular free calcium and tyrosine phosphoryla tion of a 25-kDa protein in DC. The results thus indicate that CD43 cross-l inking with specific ligands induces activation and functional maturation o f DC.