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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.

为探讨HAM的病理机制，对5例HAM尸检进行了神经病理学分析。半数以上浸润细胞泛T细胞标记阳性。病程短者CD 4阳性细胞数与CD 8阳性细胞数相等。病程较长者CD 8高于CD 4。自然杀伤细胞、IL-2 R阳性细胞和B细胞在任何阶段都很少出现。部分浸润细胞、小胶质细胞和内皮细胞呈HLA-ABC或HLA-DR阳性。在活动性炎症病变的部分巨噬细胞、星形胶质细胞和小胶质细胞中检测到IL-1 β、TNF-α和IFN-γ等多种细胞因子。从受影响的脊髓中提取DNA，通过定量PCR估计HTLV-I前病毒DNA的拷贝数为0.4至20拷贝/1000个组织细胞，并且与浸润的CD 4阳性细胞的数目良好相关。从这些发现可以看出，HAM患者脊髓中的免疫应答沿着疾病的持续时间而逐渐改变，这与HTLV-I前病毒DNA量的减少有关。通过与来源于HAM患者CSF淋巴细胞的人HTLV-I感染细胞系共培养来建立HTLV-I感染的绒猴淋巴细胞系，这些细胞的静脉内自体或异体输血导致普通绒猴中HTLV-I的持续感染。动物尚未显示神经缺陷的临床体征，然而，这可能成为HTLV-I相关疾病的有用动物模型。