GENETIC VARIANTS AS TRACERS OF T CELL FUNCTIONS IN EAE

这项建议的目的是制定一个更明确的 了解T淋巴细胞在诱导免疫应答中的作用， 自身免疫性疾病、实验性过敏性脑脊髓炎（EAE）。 EAE是一种中枢神经系统的麻痹性炎症性疾病 中枢神经系统（CNS），在许多方面类似于 最常见的人类脱髓鞘疾病，多发性硬化症（MS）。 最近发展的收养转移制度使之成为可能， 现在在小鼠中诱导疾病的慢性复发期。 本研究将采用遗传学、免疫化学和T淋巴细胞 克隆技术，以建立身份或血统关系 转移的细胞和位于 CNS病变部位。 这很重要，因为虽然T 淋巴细胞在EAE的诱导中被暗示， EAE诱导的机制仍不清楚。 的设计 实验利用了小鼠T淋巴细胞 特征性表达细胞表面抗原Thy-1。 虽然 这种抗原也在一些神经细胞上表达， 这种抗原的等位基因形式仍然使其成为一种有用的标记， 细胞贩卖研究 通过过继转移Thy-1.2+ MBP- 特异性T淋巴细胞克隆入幼稚Thy-1.1+同源基因 受体中转移细胞的迁移模式 可以跟踪收件人。 受体的冷冻CNS切片 在瘫痪发作之前，期间和之后，将检查 通过免疫过氧化物酶染色检测转移细胞的存在 技术. 辐射和抗la治疗等因素将 以确定其对移徙模式的影响， 供体细胞 最近的研究表明，中枢神经系统的淋巴细胞 损伤部位可以在体外培养和克隆。 表征 在Thy-1标记，抗原特异性， 淋巴因子的产生和致脑炎性将揭示 这些细胞与供体细胞有关， 宿主的T淋巴细胞参与了 疾病 这些实验在应用的时候更加重要 到疾病的慢性复发阶段。 迁徙 供体和宿主细胞在移植过程中的模式和功能 将研究缓解-复发周期。 实验设计 以确定供体T淋巴细胞是否迁移进出 中枢神经系统在周期和宿主来源的可能性 抑制性T淋巴细胞抑制炎症反应， 暂时缓解 这些研究将提供 更好地理解MS的潜在机制。

The objective of this proposal is to develop a clearer understanding of the roles of T lymphocytes in the induction of the autoimmune disease, experimental allergic encephalomyelitis (EAE). EAE is a paralytic and inflammatory disease of the central nervous system (CNS) and in many respects resembles the pathology of the most common human demyelinating disease, multiple sclerosis (MS). Recent development of an adoptive transfer system makes it possible now to induce chronic relapsing phases of the disease in mice. This study will use genetic, immunochemical and T lymphocyte cloning techniques to establish identity or lineage relationship between the transferred cells and the T lymphocytes localized at the CNS lesion sites. This is significant because while T lymphocytes have been implied in the induction of EAE, the mechanisms of EAE induction remain unclear. The design of the experiments takes advantage of the fact that murine T lymphocytes characteristically express a cell surface antigen, Thy-l. Although this antigen is also expressed on some neural cells, the existence of allelic forms of this antigen still makes it a useful marker for cell trafficking studies. By adoptively transferring Thy-1.2+ MBP- specific T lymphocyte clones into naive Thy-1.1+ congenic recipients, the migratory pattern of the transferred cells in the recipients can be followed. Frozen CNS sections of recipients before, during, and after the paralytic attack will be examined for the presence of the transferred cell by immunoperoxidase staining techniques. Factors such as irradiation and anti-la treatment will be examine, to determine their effects on the migratory pattern of donor cells. Recent studies show that lymphocytes localized at CNS lesion sites can be cultured and cloned in vitro. Characterization of these clones in terms of the Thy-l marker, antigen specificity, lymphokine production and encephalitogenicity will reveal whether these cells are related to the donor cells and the extent of the host's T lymphocyte participation in the manifestation of the disease. These experiments are even more important when applied to the chronic relapsing phase of the disease. The migratory pattern and functions of both the donor and host cells during the remission-relapse cycles will be studied. Experiments are designed to determine whether donor T lymphocytes migrate in and out of the CNS during the cycles and the possibility of a host-derived suppressor T lymphocyte dampening the inflammatory response during temporary remission. Taken together, these studies will provide a better appreciation of the underlying mechanisms of MS.