CNS MICROVASCULAR PERICYTE AND EAE

多发性硬化症(MS)的组织病理学特征是一个或多个白细胞亚群穿过血脑屏障(BBB)进入实质组织，导致脱髓鞘和斑块形成。现在已经知道，移民涉及到一种允许的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相互作用机制的结果。虽然有大量关于EC和星形胶质细胞生物生理学的文献，但对PC所起的作用知之甚少。我们开发了分离原代PC的技术，并努力研究其在白细胞-BBB相互作用中的作用。此前的研究表明，PC具有免疫潜力。它们表达黏附分子，合成和释放各种细胞因子。在体内、MS组织和体外，白细胞似乎聚集在PC周围。我们质疑PC是否参与了EAE的T细胞启动。银染大鼠和小鼠的CD_4脾T细胞与培养的PC黏附。具有与T1细胞一致的细胞因子分泌表型的CD4T细胞很容易与未激活的PC黏附，而T2细胞则不能。活化的PC依附于两种分泌细胞因子的表型。PC呈递抗原给预置的白细胞，表达共刺激分子，并能将记忆效应细胞重新刺激为T1或T2表型。我们认为PC可能参与炎症性中枢神经系统疾病(如MS)中跨越血脑屏障的白细胞的选择和极化。我们将研究它们在抗原特异性TCR转基因小鼠初级效应细胞的诱导中的作用，以及在启动动物记忆对记忆效应细胞的重新刺激中的作用。PC细胞因子的潜在作用将被研究。

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.