title: Monocyte-derived CD40 expression is regulated by interferon-γ/interferon-γ receptor-1 pathway when acting as a bridge during their interaction with T cells and allogeneic endothelial cells.
abstract: Previous studies have showed the lack of CD40 expression on monocytes during monocyte and endothelial cell (EC) interaction in the absence of T cells indicating that the interaction between T cells, monocytes, and ECs is required for monocyte-derived CD40 expression. We investigated the role of monocytes acting as a bridge between ECs and T cells and the possible mechanisms for monocyte-derived CD40 up-regulation in allogeneic immune responses. A coculture system with tanswell was established between purified monocytes, T cells, and ECs, and the cells were analyzed by flow cytometry to detect monocyte-derived CD40 expression. Purified monocytes stimulated by ECs did not show up-regulation of CD40 expression. Ec-stimulated monocytes up-regulated interferon (IFN)-γ receptor-1 expression. Monocytes, stimulated by ECs, up-regulated CD40 expression in the presence of T cells. However, when T cells were separated from monocyte-EC interaction, these monocytes did not show CD40 up-regulation. Furthermore, IFN-γ receptor-1 blockade but not IFN-γ receptor-2 blockade inhibited monocyte-derived CD40 expression during monocyte-EC-T cell interaction. Neutralizing antibody directed to IFN-γ inhibited up-regulation of monocyte-derived CD40. We showed here that the interaction between T cells and EC-stimulated monocytes and up-regulation of monocyte-derived CD40 expression are contact-dependent, suggesting that monocytes act as bridge between ECs and T cells. The IFN-γ receptor-1 blockade inhibited the monocyte-derived CD40 up-regulation. These data suggest that the Th1 lymphocytes provide help for monocytes via IFN-γ and IFN-γ receptor-1 pathway following their interaction.
authors.affiliation: Department of Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, P.R. China.
authors.forename: L M
authors.initials: LM
authors.lastname: Zhu
authors.forename: Y S
authors.initials: YS
authors.lastname: Fang
authors.forename: Z G
authors.initials: ZG
authors.lastname: Sun
authors.forename: L Z
authors.initials: LZ
authors.lastname: Yu
authors.forename: H
authors.initials: H
authors.lastname: Xu
mesh_terms: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D019013:CD40 Antigens / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D017471:Receptors, Interferon / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D019013:CD40 Antigens; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C086185:IFNGR2 protein, human