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The role of HHV-6 and HHV-7 in the pathogenesis of Sjogren syndrome.

HHV-6 和 HHV-7 在干燥综合征发病机制中的作用。

基本信息

批准号：
05670429
负责人：
TAKEDA Akira
金额：
$ 1.34万
依托单位：
Jichi Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
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-05670429/
关键词：
Autoimmunity Sjogren Syndrome HHV-6 HHV-7 T cell clone シェーグレン症候群

项目摘要

This research project was aimed to define the role of HHV-6 and HHV-7 in the pathogenesis of Sjogren syndrome especially from the point of view of virus specific cellular immune responses.1 We have isolated salivary glands-infiltrating T lymphocytes from minor salivary glands obtained by lip biopsy from the patients with Sjogren syndrome, and expanded them in vitro with IL2 to be rendered to the examination for the HHV-6 or HHV-7 specific T cell proliferative responses. Autologous PBMC which were sensitized with sonicated antigens made from HHV-infected CBMC (cord blood mononuclear cells) were used to stimulate those T cells. We found neither responsiveness of the T cells from minor salivary glands to the HHV-6 nor HHV-7 antigens.2 We have obtained sera from the patients with Sjogren syndrome and the normal individuals to examine for the titers of the antibodies to HHV-6 and HHV-7 by the immunofluorescence assay using virus-infected CBMC as well as the ELISA we have developed. The levels of the antibodies to HHV-6 and HHV-7 in the sera from Sjogren patients were found to be higher than those in normal individuals.The way we used in this wotk provided a unique approach to the detection or identification of the immunopathological antigens involved in the pathogenesis of autoimmune diseases. This work showed the absence of HHV-6 and HHV-7 specific T cell immune responses in the local development of the lesion in salivary glands of Sjogren patients although the high levels of antibodies to the HHV-6 and HHV-7 in the patients suggested some pathological link between the disease and the infection with those viruses in terms of the systemic humoral immunity.

本研究旨在从病毒特异性细胞免疫应答的角度探讨HHV-6和HHV-7在干燥综合征发病机制中的作用。1.我们从干燥综合征患者唇部活检获得的小涎腺中分离出浸润性唾液腺T细胞，并在体外用IL2进行扩增，以检测HHV-6或HHV-7特异性T细胞的增殖反应。用HHV感染的脐血单个核细胞(CBMC)制成的超声抗原致敏的自体PBMC刺激T细胞。我们发现小涎腺T细胞对HHV-6和HHV-7抗原均无反应性。2.我们用病毒感染的CBMC免疫荧光法和我们建立的酶联免疫吸附试验检测了干燥综合征患者和正常人血清中HHV-6和HHV-7抗体的效价。干燥病人血清中的HHV-6和HHV-7抗体水平高于正常人，为检测或鉴定自身免疫性疾病发病机制中的免疫病理抗原提供了一种独特的方法。这项工作表明，在干燥患者唾液腺病变的局部发展过程中，缺乏HHV-6和HHV-7特异性T细胞免疫反应，尽管患者体内高水平的HHV-6和HHV-7抗体表明，从系统体液免疫的角度来看，疾病与感染这些病毒之间存在一定的病理联系。