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- 介导的脱髓鞘条件，并作为一种实验模型 人类疾病多发性硬化症(MS)。先前的免疫细胞化学 对大鼠急性EAE的研究表明血管周围 免疫(CD4+)细胞向中枢神经系统的渗透 (CNS)。中枢神经系统内皮细胞的变化与血脑屏障损伤 发生在急性和慢性复发性EAE中。来自中国的研究 我们知道炎症性疾病模型中的这些变化 内皮，宽泛地称为“内皮细胞激活”，通常是 细胞因子在白细胞内皮细胞中的重要作用 相互作用，以及由此产生的白细胞迁移到 发炎。我们认为EC的激活是 Lewis大鼠急性EAE的诱导和恢复。在具体目标#1中 和#2，我们将检测细胞因子和白细胞介导的EC激活 刘易斯老鼠。活化的EC在细胞上表达活化抗原 浮出水面。细胞因子对EC激活抗原表达的影响 白细胞共培养将在完整的CNS微血管和 激光共聚焦细胞术和免疫荧光法检测EC原代培养 流式细胞术。具体目标#3和#4将检查EC的表达 激活抗原和对共培养的反应通过 急性EAE的诱导和康复。重点将放在 CD4+抑制细胞在康复中的潜在作用。特别是，我们 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.