Pathogenesis of MHV-induced demyelination

MHV 诱导的脱髓鞘的发病机制

• 批准号: 6779113
• 负责人: Ajai Dandekar
• 金额: $ 2.74万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-19 至 2005-12-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6779113
• 关键词: B lymphocyte; antibody formation; athymic mouse; disease /disorder model; laboratory mouse; leukocyte activation /transformation; multiple sclerosis; murine hepatitis virus; myelinopathy; nervous system infection; pathologic process

DESCRIPTION (provided by applicant): C57B1/6 (B6) mice infected with mouse hepatitis virus, strain JHM (MHV) develop either an acute encephalitis or chronic demyelinating disease. This demyelinating disease is a model for the human disease multiple sclerosis. We are interested in the immunological mediators of demyelination in this model. In our model, a percentage of mice protected from the acute encephalitis by maternal antibody develop a demyelinating disease We have previously observed in this model of demyelination that roughly twenty percent of the lymphocytes infiltrating the CNS are B cells, although no serum antibody can be measured in these mice. Additionally, nude (athymic) mice develop a demyelinating disease in which some 70 percent of lymphocytes in the CNS are B cells. The function of these B cells has not been characterized. In order to investigate the role of these cells in demyelination, three specific aims will be pursued: 1) To characterize the nature of the B cell response in the MHV-infected CNS; 2) To investigate failure of antibody production in the chronic demyelinating disease; and 3) To determine the immunological effectors of MHV-JHM disease in nude mice.

描述（由申请方提供）：感染小鼠的C57 B1/6（B6）小鼠 肝炎病毒JHM株（MHV）发展为急性脑炎或 慢性脱髓鞘疾病这种脱髓鞘疾病是 人类疾病多发性硬化症我们感兴趣的是 脱髓鞘的介质。在我们的模型中， 保护免受急性脑炎的母源抗体发展 脱髓鞘疾病我们以前在这个模型中观察到， 脱髓鞘，大约百分之二十的淋巴细胞浸润 CNS是B细胞，尽管在这些小鼠中不能测量血清抗体。 此外，裸（无胸腺）小鼠发展出脱髓鞘疾病，其中一些脱髓鞘疾病是由神经系统引起的。 中枢神经系统中70%的淋巴细胞是B细胞。这些B细胞的功能 还没有被定性。为了研究这些细胞在 脱髓鞘，将追求三个具体目标：1）表征脱髓鞘的细胞， MHV感染CNS中B细胞应答的性质; 2）研究 慢性脱髓鞘疾病中抗体产生的失败;和3） 在裸鼠中确定MHV-JHM病的免疫效应物。