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

本研究旨在明确HHV-6和HHV-7在干燥综合征发病机制中的作用，特别是从病毒特异性细胞免疫反应的角度。1我们从干燥综合征患者的唇活检获得的小唾液腺中分离唾液腺浸润T淋巴细胞，并在体外用IL-2扩增它们，以用于检测HHV-6或HHV-7特异性T细胞增殖应答。用由HHV感染的CBMC（脐带血单个核细胞）制成的超声处理抗原致敏的自体PBMC用于刺激这些T细胞。我们没有发现小唾液腺的T细胞对HHV-6和HHV-7抗原的反应性。2我们从干燥综合征患者和正常人中获得血清，通过使用病毒感染的CBMC的免疫荧光测定以及我们开发的ELISA来检测HHV-6和HHV-7抗体的滴度。结果表明，Sjogren患者血清中抗HHV-6和HHV-7抗体水平明显高于正常人，为检测和鉴定与自身免疫性疾病发病有关的免疫病理抗原提供了一种独特的方法。这项工作表明，HHV-6和HHV-7特异性T细胞免疫反应的缺乏在局部发展的病变在Sjogren患者的唾液腺，虽然高水平的抗体的HHV-6和HHV-7的患者提出了一些病理联系的疾病和感染这些病毒的系统性体液免疫。

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.