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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.

人类嗜t淋巴病毒1型（HTLV-I）与htlv相关性脊髓病（HAM）、关节炎、葡萄膜炎和支气管肺泡炎密切相关。HTLV-I感染引起的免疫改变可能影响病情，但其病理机制尚不清楚。为了阐明这些疾病的发病机制，建立动物模型是十分重要的。虽然有报道通过HTLV-I实验性感染WKA大鼠诱导ham样截瘫，但在这些动物中未观察到炎症变化或免疫反应改变。此外，htlv - 1转基因小鼠或大鼠已被报道可诱导类风湿性关节炎（RA）样而非ham样脊髓病。我们从HAM患者身上建立了许多htlv感染的T细胞系。其中一种（Fuk系）接种于WKA大鼠引起ra样关节炎。另一方面，当将来自ATL患者的htlv感染的T细胞系MT-2接种到WAK大鼠时，它们发生了髓神经病变。这些发现表明临床表达部分取决于接种的htlv感染细胞系。近年来，制备HTLV-I的感染性cDNA克隆在技术上已成为可能。因此，我们试图分别从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起关键作用。我们对MT-2和Fuk系HTLV-I原病毒DNA进行测序，发现HTLV-I衍生自Fuk细胞的pX区有几个产生氨基酸取代的突变。目前正在对每个细胞系的HTLV-I进行cDNA克隆感染。