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Unusual increase of extrathymic T cells in the liver of autoimmune MRL-1pr/1pr mice.

自身免疫 MRL-1pr/1pr 小鼠肝脏中胸腺外 T 细胞异常增加。

基本信息

批准号：
05454202
负责人：
KUMAGAI Katsuo
金额：
$ 3.01万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454202/
关键词：
MRL 1pr mice IL-6 ICAM-1 Liver Autoimmune disease MRL-1prマウス MRL-lpr lprマウス

项目摘要

MRL/1pr mice, which are a model of SLE and rheumatoid arthritis in humans, develop profound lymphadenopathy resulting from the accumulation of CD3^+ 4^- 8^- double-negative (DN) alpha beta T cells in peripheral lymphoid tissues. We previously indicated that these DN alpha beta T cells preferentially proliferate in the liver and migrate to the periphery. In this study, we analyzed whether any kind of cytokine was produced by hepatic mononuclear cells (MNC) in MRL/1pr mice. The evidence obtained indicates that interleukin 6 (IL-6) was vigorously produced by hepatic MNC in diseased MRL/1pr mice under unstimulated conditions. MNC in the spleen of these mice produced small amounts of IL-6, while those in the lymph nodes did not produce any appreciable amounts of IL-6. These activities of hepatic MNC in diseased MRL/1pr mice were almost completely neutralized by anti-mouse IL-6 monoclonal antibody (mAb).On the other hand, immunohistochemical staining of light-and electron-microscopic analyzes revealed that the intracellular cell abhesion molecule 1 (ICAM-1) was expressed on the hepatic sinusoidal endothelial cells of diseased MRL/1pr mice. Moreover, ICAM-1 was newly induced in the hepatic sinusoids of control C3H/He mice by an intravenous injection of 50 units of recombinant mouse IL-6. These data suggest that ICAM-1 expressed on the hepatic sinusoidal endothelial cells in MRL/1pr mice is induced by IL-6, which is produced by hepatic MNC,and that such ICAM-1 may be responsible for the saturation of inflammatory cells and the proliferation of lymphocytes in the liver of MRL/1pr mice.

MRL/1 pr小鼠是人类SLE和类风湿性关节炎的模型，由于CD 3 ^+ 4^- 8^-双阴性（DN）α β T细胞在外周淋巴组织中蓄积，导致严重的淋巴结病。我们先前指出，这些DN α β T细胞优先在肝脏中增殖并迁移到外周。本研究分析了MRL/1 pr小鼠肝脏单个核细胞（MNC）是否产生细胞因子。所获得的证据表明，白细胞介素6（IL-6）在非刺激条件下，在患病的MRL/1 pr小鼠的肝脏MNC的大力生产。这些小鼠脾脏中的MNC产生少量的IL-6，而淋巴结中的MNC不产生任何可观量的IL-6。免疫组化光镜和电镜分析显示，MRL/1 pr小鼠肝窦内皮细胞表达细胞间粘附分子1（ICAM-1）。此外，通过静脉注射50单位的重组小鼠IL-6，在对照C3 H/He小鼠的肝窦中新诱导ICAM-1。这些结果提示，MRL/1 pr小鼠肝窦内皮细胞上ICAM-1的表达是由肝脏MNC产生的IL-6诱导的，这种ICAM-1可能与MRL/1 pr小鼠肝脏炎症细胞的饱和和淋巴细胞的增殖有关。