IFN-γ-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKL
IFN-γ-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKL
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DOI：
10.1002/eji.200526141
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发表时间：
2005-11-01
影响因子：
5.4
通讯作者：
Kamatani, N
中科院分区：
文献类型：
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作者：
Kotake, S;Nanke, Y;Kamatani, N
目前的研究探讨了我们的假设，IFN-γ产生的人类T细胞抑制人类破骨细胞的形成。将来源于人PBMC的活化T细胞分为产生IFN-γ的T细胞（IFN-γ（+）T细胞）和不产生IFN-γ的T细胞（IFN-γ（-）T细胞）。IFN-γ（+）T细胞与人单核细胞在单独的巨噬细胞-CSF存在下培养。通过ELISA测量可溶性NF-κ B配体受体激活剂（RANKL）和IFN-γ的浓度以及T细胞上表达的膜型RANKL的量。在早期类风湿关节炎（RA）患者中，单独使用非甾体类抗炎药治疗，通过流式细胞术检测同时表达IFN-γ和RANKL的CD 4（+）T细胞。令人惊讶的是，IFN-γ（+）T细胞，而不是IFN-γ（-）细胞，诱导单核细胞的破骨细胞生成，其被加入骨保护素完全抑制，并通过加入抗IFN-γ抗体增加。IFN-γ（+）T细胞中可溶性和膜型RANKL的水平均升高。RA患者外周血单个核细胞（PBMC）总CD 4（+）T细胞中同时表达IFN-γ和RANKL的CD 4（+）T细胞比例升高。与我们的假设相反，IFN-γ（+）人T细胞通过表达RANKL诱导破骨细胞生成，表明Th 1细胞在Th 1优势疾病（如RA）的骨吸收中发挥直接作用。
The current study explored our hypothesis that IFN-gamma-producing human T cells inhibit human osteoclast formation. Activated T cells derived from human PBMC were divided into IFN-gamma-producing T cells (IFN-gamma(+) T cells) and IFN-gamma-non-producing T cells (IFN-gamma(-) T cells). IFN-gamma(+) T cells were cultured with human monocytes in the presence of macrophage-CSF alone. The concentration of soluble receptor activator of NF-kappa B ligand (RANKL) and IFN-gamma, and the amount of membrane type RANKL expressed on T cells, were measured by ELISA. In the patients with early rheumatoid arthritis (RA) treated with non-steroidal anti-inflammatory drugs alone, CD4(+) T cells expressing both IFN-gamma and RANKL were detected by flow cytometry. Surprisingly, IFN-gamma(+) T cells, but not IFN-gamma(-) cells, induced osteoclastogenesis from monocytes, which was completely inhibited by adding osteoprotegerin and increased by adding anti-IFN-gamma antibodies. The levels of both soluble and membrane type RANKL were elevated in IFN-gamma(+) T cells. The ratio of CD4(+) T cells expressing both IFN-gamma and RANKL in total CD4(+) T cells from PBMC was elevated in RA patients. Contrary to our hypothesis, IFN-gamma(+) human T cells induced osteoclastogenesis through the expression of RANKL, suggesting that Th1 cells play a direct role in bone resorption in Th1 dominant diseases such as RA.