Pathogenesis of HTLV-I-associated Myelopathy (HAM) ; Neuropathological Analysis and Establishment of Animal Model

HTLV-I 相关脊髓病 (HAM) 的发病机制；

基本信息

批准号：
04670494
负责人：
IZUMO Shuji
金额：
$ 0.26万
依托单位：
KAHOSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

项目摘要

A neuropathological analysis was performed in five autopsycases with HAM in order to clarify the pathomechanism of HAM.Histopathological findings revealed a chronic inflammatory process mainly involving the thoracic spinal cord. More than half of the infiltrated cells were positive for pan-T cell marker. The numbers of CD4 positive cells and CD8 positive cells were equally in the cases with short clinical course. CD8, however, was predominated over CD4 in the cases with longer duration of illness. Natural killer cells, IL-2R positive cells and B cells were rarely present at any stages. Some infiltrating cells, microglia and endotherial cells were positive for HLA-ABC or HLA-DR.Several cytokines such as IL-1beta, TNF-alpha, and IFN-gamma, were detected in some macrophages, astrocytes, and microglias in active inflammatory lesions. Copy numbers of HTLV-I proviral DNA estimated by quantitative PCR of extracted DNA from the affected spinal cords were 0.4 to 20 copies/1000 tissue cells, and were well correlated with the numbers of infiltrated CD4 positive cells. From these findings it is suggested that immune responses in the spinal cord of HAM patients gradually change along with the duration of illness in correlation with the decreasing amount of HTLV-I proviral DNA.HTLV-I infected marmoset lymphocytes lines were established by co-culture with a human HTLV-I infected cell line derived from CSF lymphocytes of a HAM patient, and intravenous auto- or allotransfusion of these cells resulted persistent infection of HTLV-I in common marmosets. The animals show no clinical signs of neurological deficits yet, however, this may become a useful animal model of HTLV-I associated diseases.

为了阐明HAM机制的五个尸体病房，进行了神经病理学分析。组织病理学的发现表明，慢性炎症过程主要涉及胸椎脊髓。 Pan-T细胞标记物中超过一半的浸润细胞为阳性。在临床疗程短的情况下，CD4阳性细胞和CD8阳性细胞的数量平均。然而，在疾病持续时间更长的情况下，CD8占CD4的占主导地位。天然杀伤细胞，IL-2R阳性细胞和B细胞在任何阶段很少存在。在某些巨噬细胞，星形胶质细胞和微胶质细胞中检测到一些浸润细胞，小胶质细胞和hla-abc或HLA-DR。诸如IL-1BETA，TNF-ALPHA和IFN-GAMMA之类的诸如IL-1BETA，TNF-ALPHA和IFN-GAMMA之类的几个细胞因子为阳性的阳性。。通过从受影响的脊髓提取的DNA定量PCR估计的HTLV-I病毒DNA的拷贝数为0.4至20份/1000个组织细胞，并且与浸润的CD4阳性细胞的数量很好地相关。从这些发现中提出，HAM患者的脊髓中的免疫反应随着疾病的持续时间逐渐变化，与htlv-i前病毒DNA的量减少相关。与人类HTLV-1感染的细胞系具有源自HAM患者CSF淋巴细胞的细胞系，以及这些细胞的静脉内自身灌注或同异吞和同酶引起的，导致了普通果会中HTLV-I的持续感染。这些动物尚未显示出神经系统缺陷的临床迹象，但是，这可能成为HTLV-I相关疾病的有用动物模型。