GENETIC VARIANTS AS TRACERS OF T CELL FUNCTIONS IN EAE

这项提议的目标是制定一项更明确的 对T淋巴细胞在慢性粒细胞白血病诱导中作用的认识 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和炎症性疾病。 系统(CNS)，在许多方面类似于 人类最常见的脱髓鞘疾病，多发性硬化症(MS)。 最近开发的收养转移系统使这成为可能 现在要在老鼠身上诱导疾病的慢性复发期。 这项研究将使用遗传、免疫化学和T淋巴细胞 建立身份或血统关系的克隆技术 在转移细胞和T淋巴细胞之间定位于 中枢神经系统损害部位。这一点意义重大，因为虽然T 淋巴细胞在EAE的诱导中起到了一定的作用 EAE的诱导机制尚不清楚。这款车的设计 实验利用了这样一个事实，即小鼠T淋巴细胞 特有地表达一种细胞表面抗原，Thy-L。虽然 这种抗原也表达在一些神经细胞上，存在 这种抗原的等位基因形式仍然使其成为一种有用的标记 细胞贩运研究。通过过继转移THY-1.2 MBP- 特异性T淋巴细胞克隆入单纯Thy-1.1同源基因 受者体内转移细胞的迁移模式 收件人可以被跟踪。受者的中枢神经系统冰冻切片 在瘫痪发作之前、期间和之后将检查 免疫过氧化物酶染色检测转移细胞的存在 技巧。辐射和抗LA治疗等因素将 被审查，以确定它们对移民模式的影响 捐献细胞。最近的研究表明，淋巴细胞定位于中枢神经系统 病变部位可以在体外培养和克隆。表征 在这些克隆中，根据Thy-L标记，抗原特异性， 淋巴因子的产生和脑源性将揭示 这些细胞与供体细胞和供体细胞 宿主T淋巴细胞参与慢性粒细胞白血病的临床表现 疾病。这些实验在应用时甚至更重要 到疾病的慢性复发阶段。迁徙的 供体细胞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。设计了实验 确定供者T淋巴细胞是否迁入和迁出 循环期间CNS和宿主派生的可能性 抑制性T淋巴细胞抑制炎症反应 暂时缓解。总而言之，这些研究将提供 更好地了解多发性硬化症的基本机制。

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.