ACUTE EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS-- ENDOTHELIAL ACTIVATION ANTIGEN

实验性自身免疫性脑脊髓炎（EAE）是一种T淋巴细胞- 介导的脱髓鞘疾病，并作为实验模型， 多发性硬化症（MS）。 既往免疫细胞化学 对大鼠急性EAE的研究表明， 免疫（CD 4+）细胞浸润到中枢神经系统 （CNS）。 中枢神经系统内皮细胞变化与血脑屏障损伤 发生在急性和慢性复发性EAE中。 研究中的 炎症性疾病模型，我们知道这些变化， 内皮细胞，不严格地称为“内皮细胞活化”， 白细胞-内皮细胞介导的重要作用 相互作用，以及由此产生的白细胞迁移到 炎症 我们认为EC激活是一个重要的步骤， 急性EAE诱导和刘易斯大鼠的恢复。 具体目标#1 和#2，我们将检查细胞因子和白细胞介导的EC激活， 刘易斯大鼠。 活化的EC表达细胞表面的活化抗原 面 细胞因子诱导EC活化抗原的表达 和白细胞共培养将在完整的CNS微血管上测量， 使用共聚焦激光细胞术和免疫荧光的EC原代培养 流式细胞仪 具体目标#3和#4将检查EC表达， 活化抗原和对共培养物的应答， 从急性EAE中诱导和恢复。 重点将放在 CD 4+抑制细胞在恢复中的潜在作用。 我们尤其 将研究Ts与EC可能的相互作用。

Experimental autoimmune encephalomyelitis (EAE) is a T-Lymphocyte- mediated demyelinating condition and serves as an experimental model of the human disease multiple sclerosis (MS). Previous immunocytochemical studies of acute EAE in the rat have demonstrated perivascular infiltration of immune (CD4+) cells into the central nervous system (CNS). Changes in CNS endothelium as well as blood brain barrier injury occurs in both acute and chronic relapsing EAE. From studies in inflammatory disease models we know that these changes in the endothelium, loosely termed "endothelial cell activation", are often cytokine-mediated and important in leukocyte-endothelial cell interaction, and the resultant migration of leukocytes into sites of inflammation. We propose that EC activation is an important step in acute EAE induction and recovery in the Lewis rat. In specific aim #1 and #2, we will examine cytokine and leukocyte mediated EC activation in Lewis rats. Activated EC express activation antigens on the cell surface. Expression of EC activation antigens in response to cytokines and leukocyte co-culture will be measured on intact CNS microvessels and EC primary cultures using confocal laser cytometry and immunofluorescence flow cytometry. Specific aims #3 and #4 will examine EC expression of activation antigens and response to co-culture sequentially through induction and recovery from acute EAE. Emphasis will be placed on the potential role of CD4+ suppressor cells in recovery. In particular, we will study possible interactions of Ts with EC.