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.
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.
Zhu, LM; Fang, YS; Sun, ZG; Yu, LZ; Xu, H
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