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Indirect recruitment of a CD40 signaling pathway in dendritic cells by B7-DC cross-linking antibody modulates T cell functions.
PLoS One
July 2009
Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN, USA.
The human IgM B7-DC XAb protects mice from tumors in both therapeutic and prophylactic settings. Its mechanism of action is mediated by its binding to B7-DC/PD-L2 molecules on the surface of dendritic cells (DCs) to induce a multimolecular cap and subsequent activation of signaling cascades that determine a unique combination of DC phenotypes. One such phenotype, the B7-DC XAb-induced antigen accumulation in mTLR-matured DCs, has been linked to signaling through TREM-2, but the signals required for other DC phenotypes critical for the therapeutic effects in animal models remain unclear.
View Article and Find Full Text PDFB7-DC/PD-L2 cross-linking induces NF-kappaB-dependent protection of dendritic cells from cell death.
J Immunol
February 2007
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Cross-linking cell surface molecules with IgM Abs is a specific approach for activating cells in vitro or in vivo. Dendritic cells (DC) activated with a human B7-DC (PD-L2)-specific IgM Ab can induce strong antitumor responses and block inflammatory airway disease in experimental models, yet the Ab-mediated molecular events promoting these responses remain unclear. Analysis of human or mouse DC treated with the B7-DC cross-linking Ab revealed PI3K-dependent phosphorylation of AKT accompanied by mobilization of NF-kappaB.
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