IMMUNOGENETICS OF DEMYELINATION

该项目的主要目标是研究脱髓鞘和神经功能缺陷的免疫遗传学基础。实验将利用人类多发性硬化症的两个优秀模型，即泰勒氏病毒感染和实验性自身免疫性脑脊髓炎。该项目由梅奥医学院神经学和免疫学教授摩西·罗德里格斯博士指导，他长期以来一直对人类多发性硬化症的脱髓鞘和重新髓鞘形成的发病机制感兴趣。该项目的成员(Chella S.David博士、Larry R.Pease博士和摩西·罗德里格斯博士)都是梅奥医学院的知名研究人员和免疫学教授。该小组在人类疾病的小鼠模型中的免疫遗传学研究方面有着令人印象深刻的记录。项目1：(首席研究员罗德里格斯博士)将研究泰勒氏病毒基因组在小鼠体内的转基因表达。这些实验还将探讨在人类人类白细胞抗原转基因小鼠中观察到的减少脱髓鞘疾病的机制，并解决在脱髓鞘后功能性神经功能障碍的发生中重要的致病免疫反应的特异性。项目2：(首席研究员皮斯博士)将研究中枢神经系统中抗TMEV淋巴细胞反应的H-2K和H-2D极性的基础。实验将确定病毒特异性CD8T细胞在抵抗持续病毒感染和神经病理学中的重要性。项目3：(首席研究员David博士)将研究表达HLA-DR或DQ单倍型的实验性自身免疫性脑脊髓炎。实验将研究人类白细胞抗原DR和DQ分子与多发性硬化症相关的自身抗原。这一项目由一组高度互动的研究人员专注于脱髓鞘的免疫遗传学基础，有望为多发性硬化症的髓鞘和神经损伤的发病机制提供新的见解。

The major goal of this program project is to investigate the immunogenetic basis of demyelination and neurological deficits. The experiments will utilize two excellent models of human multiple sclerosis, i.e. Theiler's virus infection and experimental autoimmune encephalomyelitis. The program project is under the direction of Dr. Moses Rodriguez Professor of Neurology and Immunology of the Mayo Medical School who has ha a long interest in the pathogenesis of demyelination and remyelination in human multiple sclerosis. Members of the Program Project (Drs. Chella S. David, Dr. Larry R. Pease, and Dr. Moses Rodriguez) are well established investigators and Professors of Immunology in the Mayo Medical School. This group has an impressive record of investigations on the immunogenetics in murine models of human disease. Project 1: (Dr. Rodriguez, Principal Investigator) will investigate transgenic expression of Theiler's virus genomes in mice. The experiments will also investigate the mechanisms of decreased demyelinating disease observed in human HLA transgenic mice and address the specificity of the pathogenic immune response important in development of functional neurological deficits following demyelination. Project 2: (Dr. Pease, Principal Investigator) will investigate the basis for H-2K vs. H-2D polarity of anti-TMEV lymphocyte responses in the central nervous system. Experiments will identify the importance of virus-specific CD8+ T cells in the resistance to persistence virus infection and in neuropathology. Project 3: (Dr. David, Principal Investigator) will investigate experimental autoimmune encephalomyelitis in HLA expressing HLA-DR or DQ haplotypes. Experiments will examine the presentation of putative autoantigens linked to MS by HLA-DR and DQ molecules. This Program Project focusing on the immunogenetic basis of demyelination by a group of highly interactive investigators is expected to provide new insights into the pathogenesis of myelin and neural injury in multiple sclerosis.