CNS MICROVASCULAR PERICYTE AND EAE

多发性硬化症（MS）的组织病理学特征是一种或多种白细胞亚群穿过血脑屏障（BBB）迁移到实质组织中，导致脱髓鞘和斑块形成。 现在已知，迁移涉及许可的BBB。 从血脑屏障的角度来看，允许迁移是血脑屏障的细胞成分、内皮细胞（EC）、周细胞（PC）和星形胶质细胞之间一系列复杂的串扰机制的结果。 虽然有大量的文献可供EC和星形胶质细胞生物生理学非常少的PC所扮演的角色。 我们已经开发出分离原发性PC的技术，并致力于研究其参与白细胞-BBB相互作用。 已有研究表明PC具有免疫潜能。 它们表达粘附分子并合成和释放多种细胞因子。 在MS组织和体外，白细胞似乎聚集在体内PC周围。 我们质疑PC是否参与EAE中的T细胞启动。 来自大鼠和小鼠的Ag致敏的CD 4脾T细胞粘附于培养的PC。具有与T1细胞一致的细胞因子分泌表型的CD 4 T细胞容易粘附于未活化的PC，而T2细胞不粘附。活化的PC粘附于两种细胞因子分泌表型。 PC将抗原呈递给致敏的白细胞，表达共刺激分子，并且可以将记忆效应细胞再刺激为T1或T2表型。 我们建议，PC可能参与选择和极化的白细胞，跨越血脑屏障的炎症性中枢神经系统疾病，如MS。我们将研究它们的作用，在银特异性TCR转基因小鼠的初级效应细胞的诱导，以及记忆TO记忆效应细胞在引发的动物的再刺激。 将检查PC细胞因子的潜在作用。

The hallmark of tissue pathology in multiple sclerosis (MS) is the migration of one or more leukocyte subsets across the blood brain barrier (BBB) into the parenchymal tissue with resultant demyelination and plaque formation. It is now known that migration involves a permissive BBB. From the standpoint of the BBB permission to migrate is the result of a complicated series of cross-talk mechanisms between the cellular constituents of the BBB, the endothelial cell (EC), the pericyte (PC), and the astrocyte. While a plethora of literature is available on EC and astrocyte biophysiology very little is known of the role played by the PC. We have developed techniques to isolate primary PC and have endeavored to study its involvement in leukocyte-BBB interactions. Previous studies have shown that PC have immune potential. They express adhesion molecules and synthesize and release a variety of cytokines. Leukocytes appear to cluster around the PC in vivo in MS tissue and in vitro. We question whether PC are involved in T-cell priming in EAE. Ag primed CD4 splenic T-cells from both rats and mice adhere to cultured PC. CD4 T-cells with a cytokine secreting phenotype consistent with T1 cells adhere readily to nonactivated PC while T2 cells do not. Activated PC adhere to both cytokine secreting phenotypes. PC present antigen to primed leukocytes, express co-stimulatory molecules and can restimulate memory effector cells to either T1 or T2 phenotype. We propose that PC may be involved in selection and polarization of leukocytes that migrate across the BBB in inflammatory CNS disorders such as MS. We will study their role in induction of primary effector cells in Ag-specific TCR transgenic mice, as well as the restimulation of memory TO to memory effector cells in primed animals. The potential role of PC cytokines will be examined.