IMMUNOGENETICS OF DEMYELINATION

本项目的主要目标是研究脱髓鞘和神经功能缺损的免疫遗传学基础。实验将利用两种优秀的人类多发性硬化症模型，即Theiler病毒感染和实验性自身免疫性脑脊髓炎。该项目是在梅奥医学院神经学和免疫学教授Moses Rodriguez博士的指导下进行的，他对人类多发性硬化症脱髓鞘和再髓鞘的发病机制有长期的兴趣。项目成员（博士）Chella S. David博士，Larry R. Pease博士和Moses Rodriguez博士)是梅奥医学院的免疫学专家和教授。这个小组在人类疾病小鼠模型的免疫遗传学研究方面有着令人印象深刻的记录。项目一：（首席研究员罗德里格斯博士）将研究Theiler病毒基因组在小鼠中的转基因表达。实验还将研究在人类HLA转基因小鼠中观察到的脱髓鞘疾病减少的机制，并解决在脱髓鞘后功能性神经功能缺陷发展中重要的致病性免疫反应的特异性。项目二：（首席研究员Dr. Pease）将研究中枢神经系统抗tmev淋巴细胞H-2K和H-2D极性反应的基础。实验将确定病毒特异性CD8+ T细胞在抵抗持久性病毒感染和神经病理学中的重要性。项目3 （David博士，首席研究员）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。实验将检验HLA-DR和DQ分子与MS相关的假定自身抗原的呈现。该项目由一组高度互动的研究人员组成，重点研究脱髓鞘的免疫遗传学基础，有望为多发性硬化症髓磷脂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.