Induction of chronic inflammatory myelopathy in rats infected with recombinant HTLV-I

重组HTLV-I感染大鼠慢性炎症性脊髓病的诱导

基本信息

批准号：
10557062
负责人：
KIRA Jun-ichi
金额：
$ 3.39万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10557062/
关键词：
HTLV-I HAM Myelopathy Arthritis animal models MT-2 infectious cDNA clone キメラ HTLV-1 感染症cDNAクローンラットクローンサイトカイン Th1 Th2バランス中枢神経末梢神経

项目摘要

Human T-lymphotropic virus type 1 (HTLV-I) is closely linked to HTLV-associated myelopathy (HAM), arthritis, uveitis and bronchial alveolitis. Immunological changes caused by HTLV-I infection may affect the condition, but the pathomechanism remains unknown. To elucidate the pathomechanism of these diseases, it is important to make animal models. Although induction of HAM-like paraparesis through experimental infection of WKA rats with HTLV-I has been reported, neither inflammatory changes nor alteration of the immune response has been observed in these animals. In addition, HTLV-I transgenic mice or rat has been reported to induce rheumatoid arthritis (RA)-like but not HAM-like myelopathy.We established many HTLV-infected T cell lines from HAM patients. One of them (Fuk line) inoculated to WKA rat caused RA-like arthritis. On the other hand, when MT-2, which is a HTLV-infected T cell line derived from ATL patient, was inoculated to WAK rats, they developed myeloneuropathy. These findings suggest that clinical expression in part depends on the HTLV-infected cell lines inoculated. Recently, it becomes technically possible to make infectious cDNA clones of HTLV-I. So, we tried to make infections cDNA clones from MT-2 cells and Fuk cells, respectively, to clarify which portion of HTLV-I genome play a pivotal role for the induction of myelopathy or arthritis. We sequenced the HTLV-I proviral DNA of MT-2 and Fuk line and found several mutations producing amino acid substitution in the pX region of HTLV-I derived from Fuk cells. It is now underway to make infections cDNA clone of HTLV-I of each cell lines.

人类T-淋巴细胞病毒1型（HTLV-I）与HTLV相关的脊髓病（HAM），关节炎，葡萄膜炎和支气管肺炎肺泡炎密切相关。由HTLV-1感染引起的免疫学变化可能会影响病情，但病理机制仍然未知。为了阐明这些疾病的病理机理，制作动物模型很重要。尽管据报道，通过用HTLV-I的WKA大鼠进行实验感染HAM样的简介，但在这些动物中均未观察到炎症变化或免疫反应的改变。此外，据报道，HTLV-I转基因小鼠或大鼠会诱导类风湿关节炎（RA） - 类似于HAM样骨髓病。我们确定了HAM患者的许多HTLV感染的T细胞系。其中之一（FUK线）接种到WKA大鼠引起了RA样关节炎。另一方面，当MT-2是源自ATL患者的HTLV感染的T细胞系的MT-2被接种到WAK大鼠时，他们就会发展出骨髓病。这些发现表明，部分临床表达部分取决于接种的HTLV感染的细胞系。最近，从技术上讲，成为HTLV-I的传染性cDNA克隆成为可能。因此，我们试图分别从MT-2细胞和FUK细胞中制作感染cDNA克隆，以阐明HTLV-I基因组的哪一部分起着诱导骨髓病或关节炎的关键作用。我们对MT-2和FUK系的HTLV-I前病毒DNA进行了测序，并发现了几种突变在源自FUK细胞的HTLV-I的PX区域产生氨基酸取代。现在正在进行中，使每种细胞系的HTLV-I的感染cDNA克隆。