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Analysis of the molecular mechanisms of the development of HAM from the point of view of Th1/Th2 balance

从Th1/Th2平衡角度分析HAM发生发展的分子机制

基本信息

批准号：
10670593
负责人：
NAKAMURA Tatsufumi
金额：
$ 2.18万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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-10670593/
关键词：
HAM CD4ィイD1+ィエD1T-lymphocytes matrix metalloproteinase-2 Th1 Th2 balance Fas Fas ligand pentoxifylline VCAM-1 VLA-4 E-selectin ligand matrix metalloproteinase-2 Th2balance T-lymphocytes Adhesion molecules

项目摘要

We investigated the molecular mechanisms of the development of HTLV-I associated myelopathy (HAM) from the point of view of Th1/Th2 balance in peripheral blood CD4+ T lymphocytes. Research results are as follows: 1) Elevated levels of interferon-γ (IFN-γ) in the sera and CSF based on elevated levels of serum IL-12 in HAM patients (J Neuroimmunol 95:185-189, 1999). 2) The fact of 1) was supported by clinical efficacy of pentoxifylline, which make up-regulation of Th2 cytokines, in treatment of HAM patients (Intern Med 38:717-721, 1999). 3) Increase of E-selectin+CD4ィイD1+ィエD1 T lymphocytes based on HTLV-I infection, which activities of IFN-γ expression are exaggerated, in peripheral blood T lymphocytes (PBT) of HAM patients (manuscript, submitted). 4) Increased Fas-madiated cytotoxicity of CD4ィイD1+ィエD1 T lymphocytes in HAM patients (J Neuroimmunol 86:198-201, 1998). 5) CD4ィイD1+ィエD1 T lymphocytes in HAM patients itself are resistant against apoptosis, under high expression of Bcl-xL which is one of anti-apoptotic protein in Fas/Fas ligand system (manuscript, submitted). 6) Matrix metalloproteinase-2 induction through VCAM-1/VLA-4 pathway is up-regulated in PBT of HAM patients (J Neuroimmunol 99:242-247, 1999). These results strongly suggest that the immunological balance of helper T lymphocytes between Th1 and Th2 is toward Th1 in the peripheral blood of HAM patients and Th1-mediated immunological status is involved in the development of HAM. In addition, the therapeutic approaches towards the correction of Th1/Th2 balance, such as pentoxifylline, might contribute to successful treatments against HAM patients.

我们从外周血CD 4 + T淋巴细胞Th 1/Th 2平衡的角度研究了HTLV-I相关性脊髓病（HAM）发生的分子机制。研究结果如下：1）基于HAM患者血清IL-12水平升高，血清和CSF中干扰素-γ（IFN-γ）水平升高（J Neuroimmunol 95：185-189，1999）。2)1）的事实得到了在治疗HAM患者中使Th 2细胞因子上调的喷替福林的临床功效的支持（Intern Med 38：717-721，1999）。3)HAM患者外周血T淋巴细胞（PBT）中基于HTLV-I感染的E-选择素+CD 4 + CD 4 + D1+ CD 4 + D1 T淋巴细胞增加，其IFN-γ表达活性被夸大（手稿，已提交）。4)HAM患者中CD 4 + CD 4 + CD 4 + D1 T淋巴细胞Fas介导的细胞毒性增加（J Neuroimmunol 86：198-201，1998）。5)HAM患者中的CD 4 + CD 4 + D1+ CD 4 + D1 + T淋巴细胞本身在Fas/Fas配体系统中的抗凋亡蛋白Bcl-xL的高表达下抗凋亡（手稿，已提交）。6)通过VCAM-1/VLA-4途径的基质金属蛋白酶-2诱导在HAM患者的PBT中上调（J Neuroimmunol 99：242-247，1999）。提示HAM患者外周血辅助性T淋巴细胞的Th 1/Th 2免疫平衡倾向于Th 1，Th 1介导的免疫状态参与了HAM的发生发展。此外，纠正Th 1/Th 2平衡的治疗方法，如戊茶碱，可能有助于成功治疗HAM患者。