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Induction of vasculitis by vascular smooth muscle-specifc T cells and analysis of its mechanism

血管平滑肌特异性T细胞诱导血管炎及其机制分析

基本信息

批准号：
06807020
负责人：
OZAKI Shoichi
金额：
$ 1.28万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06807020/
关键词：
vasculitis animal model vascular smooth muscle MRL-++ mouse CD4^+ T cells pulmonary vasculitis cytotoxicity Fas ligand MRL nマウス

项目摘要

We established a T-cell line, MV1, specific for rat vascular smooth muscle antigen from the regional lymph nodes of immunized MRL/Mp-+/+ mice. Adoptive transfer of MV1 T cells induced vasculitis lesions in the lungs of the syngeneic recipient mice pre-treated with cyclophosphamide. Flow cytometric analysis showed that MV1 was a CD4+ T cell line. The T cells proliferated in the presence of the vascular smooth muscle antigen and mitomycin C-treated syngeneic spleen cells. The cross experiments using an ovalbumin-specific T-cell line demonstrated that MV1 was specific for vascular smooth muscle antigen. The antigen-specific proliferation of MV1 was CD4 dependent, which was consistent with the flow cytometric analysis. In addition, MV1 T cells, upon activation with anti-CD3 antibody or antigen-specific activation, killed A 20.2J mouse B lymphoma cells. MV1 T cells also killed a CD95 (Fas) -transfected T lymphoma line, but not its parental Fas-negative cell line. These findings indicated that MV1 T cells killed target cells via a Fas ligand (FasL) /Fas pathway. The cytotoxicity of MV1 T cells may play an important role in the development of the vasculitis in this model. Although the antigenic epitopes of MV1 and the lung specificity of the vasculitis remain to be clarified, MV1-induced vasculitis should serve as an experimental model of human pulmonary vasculitis.

我们建立了一个T细胞系，MV 1，特异性为大鼠血管平滑肌抗原免疫MRL/Mp-+/+小鼠的区域淋巴结。MV 1 T细胞的连续转移在用环磷酰胺预处理的同基因受体小鼠的肺中诱导血管炎病变。流式细胞仪分析显示MV 1为CD 4 + T细胞系。在血管平滑肌抗原和丝裂霉素C处理的同系脾细胞的存在下，T细胞增殖。使用卵清蛋白特异性T细胞系的交叉实验证明MV 1对血管平滑肌抗原具有特异性。MV 1的抗原特异性增殖是CD 4依赖性的，这与流式细胞术分析一致。此外，MV 1 T细胞在用抗CD 3抗体活化或抗原特异性活化后，杀死A 20.2J小鼠B淋巴瘤细胞。MV 1 T细胞也杀死了CD 95（Fas）转染的T淋巴瘤细胞系，但不是其亲本Fas阴性细胞系。这些发现表明MV 1 T细胞通过Fas配体（FasL）/Fas途径杀伤靶细胞。MV 1 T细胞的细胞毒性可能在该模型中血管炎的发展中起重要作用。虽然MV 1的抗原表位和肺特异性的血管炎仍有待澄清，MV 1诱导的血管炎应作为人类肺血管炎的实验模型。