Pathogenesis of MHV-induced demyelination

MHV 诱导的脱髓鞘的发病机制

• 批准号: 6445029
• 负责人: AJAI A DANDEKAR
• 金额: $ 2.48万
• 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/6445029
• 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（由申请人提供）：感染了鼠标的C57B1/6（B6）小鼠 肝炎病毒，JHM菌株（MHV）患有急性脑炎或 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。我们对免疫学感兴趣 该模型中的脱髓鞘介体。在我们的模型中，一定比例的小鼠 孕产妇抗体免受急性脑炎的保护 我们以前在此模型中观察到的脱髓鞘疾病 脱髓鞘大约有20％的淋巴细胞渗入 中枢神经系统是B细胞，尽管在这些小鼠中无法测量血清抗体。 此外，裸（无胸腺）小鼠会发展出一种脱髓鞘疾病，其中一些疾病 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 尚未表征。为了研究这些细胞在 脱髓鞘，将追求三个具体目标：1）表征 MHV感染的中枢神经系统中B细胞反应的性质； 2）调查 慢性脱髓鞘疾病中抗体产生的衰竭；和3）到 确定裸鼠MHV-JHM疾病的免疫学效应因子。