类风湿关节炎中CD40的结扎诱导肿瘤坏死因子-α：滑膜细胞激活的新机制。

Ligation of CD40 induced tumor necrosis factor-alpha in rheumatoid arthritis: a novel mechanism of activation of synoviocytes.

作者信息

Harigai M, Hara M, Nakazawa S, Fukasawa C, Ohta S, Sugiura T, Inoue K, Kashiwazaki S

机构信息

Institute of Rheumatology, Tokyo Women's Medical University, Japan.

出版信息

J Rheumatol. 1999 May;26(5):1035-43.

PMID:10332965

Abstract

OBJECTIVE

To determine the immunopathological significance of CD40/CD40 ligand (CD40L) interaction in rheumatoid arthritis (RA).

METHODS

The expression of CD40 ligand (CD40L) in synovial tissues (ST) from patients with RA was examined by immunohistochemistry. Tumor necrosis factor-alpha (TNF-alpha) was measured by ELISA. Expression of CD40 on ST cells was quantified by anti-CD40 monoclonal antibodies and 125I labelled anti-mouse IgG.

RESULTS

Immunohistochemistry showed CD40L+ T cells in RA ST. Ligation of CD40 on RA ST cells significantly increased the production of TNF-alpha in a dose dependent fashion. Adherent, but not non-adherent, fraction of ST cells responded to ligation of CD40 to produce TNF-alpha. Interferon-gamma (IFN-gamma), interleukin 4 (IL-4), or IL-13 acted synergistically with CD40 ligation to enhance TNF-alpha production by ST cells. IL-10 exerted inhibitory effects on both CD40 ligation induced and CD40 ligation plus IFN-gamma induced TNF-alpha production by ST cells.

CONCLUSION

These data indicate activated T cells participate in synovial inflammation of RA via CD40L to stimulate the production of TNF-alpha by ST cells. The effect of CD40 ligation is modulated by the presence of several cytokines, e.g., IFN-gamma, IL-4, IL-10, and IL-13.

摘要

目的

确定CD40/CD40配体（CD40L）相互作用在类风湿关节炎（RA）中的免疫病理学意义。

方法

采用免疫组织化学法检测RA患者滑膜组织（ST）中CD40配体（CD40L）的表达。通过酶联免疫吸附测定（ELISA）检测肿瘤坏死因子-α（TNF-α）。用抗CD40单克隆抗体和125I标记的抗小鼠IgG对ST细胞上CD40的表达进行定量。

结果

免疫组织化学显示RA滑膜组织中有CD40L+T细胞。RA滑膜组织细胞上CD40的连接以剂量依赖方式显著增加TNF-α的产生。滑膜组织细胞的贴壁部分而非非贴壁部分对CD40连接产生反应以产生TNF-α。干扰素-γ（IFN-γ）、白细胞介素4（IL-4）或白细胞介素13与CD40连接协同作用，增强滑膜组织细胞产生TNF-α。IL-10对滑膜组织细胞CD40连接诱导的以及CD40连接加IFN-γ诱导的TNF-α产生均有抑制作用。