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 相关脊髓病 (HAM)、关节炎、葡萄膜炎和支气管肺泡炎密切相关。 HTLV-I感染引起的免疫学变化可能会影响病情，但病理机制仍不清楚。为了阐明这些疾病的发病机制，制作动物模型非常重要。尽管已有报道通过用 HTLV-I 实验性感染 WKA 大鼠来诱导 HAM 样截瘫，但在这些动物中尚未观察到炎症变化或免疫反应的改变。此外，据报道HTLV-I转基因小鼠或大鼠可诱发类风湿性关节炎(RA)样脊髓病，但不会诱发HAM样脊髓病。我们从HAM患者中建立了许多HTLV感染的T细胞系。其中一种（Fuk系）接种到WKA大鼠后引起RA样关节炎。另一方面，当MT-2（一种源自ATL患者的HTLV感染T细胞系）接种给WAK大鼠时，它们出现了脊髓神经病。这些发现表明，临床表达部分取决于接种的 HTLV 感染细胞系。最近，在技术上已经可以制造 HTLV-I 的感染性 cDNA 克隆。因此，我们尝试分别从 MT-2 细胞和 Fuk 细胞中克隆感染 cDNA，以阐明 HTLV-I 基因组的哪一部分在诱导脊髓病或关节炎中发挥关键作用。我们对 MT-2 和 Fuk 系的 HTLV-I 前病毒 DNA 进行了测序，发现在源自 Fuk 细胞的 HTLV-I 的 pX 区域中产生氨基酸取代的几个突变。现在正在制作每个细胞系的HTLV-I感染cDNA克隆。