Ligation of CD4 on human blood monocytes triggers macrophage differentiation (158.8)
Ligation of CD4 on human blood monocytes triggers macrophage differentiation (158.8)
复制标题
CD4 在人血单核细胞上的连接触发巨噬细胞分化 (158.8)
作者：
S. Kitchen;S. Krutzik;B. Levin;V. Rezek;C. Kitchen;J. Zack
人单核/巨噬细胞(M/M)在先天免疫反应和控制获得性免疫反应中起着重要作用。人类M/M的一个独特方面是它们表达CD4分子。CD4分子在人类单核/巨噬细胞功能和发育中的作用尚不清楚。为了研究人类M/M细胞上表达的CD4的作用，用天然的CD4配体--可溶性人类白细胞抗原II类(SHLAII)处理人血单核细胞。我们确定sHLAII：CD4结扎触发了人单核细胞分化为功能成熟的巨噬细胞。这些新形成的巨噬细胞诱导T细胞激活的能力增强，这表明这些细胞在CD4结扎后免疫功能增强。我们观察了外周血单核细胞在CD4结扎后钙离子流量以及基因和细胞因子蛋白表达的变化。这表明，CD4的结扎在这种细胞类型中传递了一个功能信号。我们发现，在原代单核细胞中，CD4的细胞内信号通过src家族激酶以及MAPK通路来触发巨噬细胞分化。我们发现，在干扰素-γ诱导的人脐静脉内皮细胞上，人类白细胞抗原II可以连接单核细胞表面的CD4，并触发这些细胞向功能性巨噬细胞的分化。总之，我们的结果确认了人类外周血单核细胞上的CD4分子在与HLAII相互作用后触发这些细胞分化为功能性巨噬细胞的新功能。
Human monocytes/macrophages (M/M) have an important role in innate immune responses and in controlling adaptive immune responses. One unique aspect of human M/M is that they express the CD4 molecule. The role of the CD4 molecule in human monocyte/macrophage function and development is not known. To investigate the role of CD4 expressed on human M/M, human blood monocytes were treated with soluble HLA Class II (sHLA II), a natural CD4 ligand. We determined that sHLA II:CD4 ligation triggered the differentiation of human monocytes into functional mature macrophages. These newly developed macrophages had an increased ability to induce T cell activation, suggesting enhanced immune function following CD4 ligation of these cells. We observed a calcium flux and the modulation of gene and cytokine protein expression following CD4 ligation on peripheral monocytes. This indicates that ligation of CD4 transmits a functional signal in this cell type. We found that intracellular signaling of CD4 in primary monocytes occurs through src family kinases as well as via the MAPK pathway to trigger macrophage differentiation. We show that HLA II on IFN-γ-induced HUVECs can ligate CD4 on monocytes and trigger differentiation of these cells into functional macrophages. In all, our results have identified a new function for the CD4 molecule on human peripheral monocytes in triggering the differentiation of these cells into functional macrophages following their interaction with HLA II.