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越过血脑屏障（BBB）迁移到实质组织，导致脱髓鞘和斑块形成。现在我们知道，迁移涉及到一个允许的血脑屏障。从血脑屏障的角度来看，允许其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。虽然有大量关于EC和星形胶质细胞生物生理学的文献，但很少有人知道PC所起的作用。我们已经开发了分离原发性PC的技术，并努力研究其与白细胞-血脑屏障相互作用的关系。先前的研究表明，PC具有免疫潜力。它们表达粘附分子，合成和释放多种细胞因子。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EAE的t细胞启动。大鼠和小鼠的CD4脾t细胞均粘附在培养的PC上。具有与T1细胞一致的细胞因子分泌表型的CD4 t细胞很容易粘附在未激活的PC上，而T2细胞则不然。活化的PC坚持两种细胞因子分泌表型。PC将抗原呈递到引物白细胞，表达共刺激分子，并能将记忆效应细胞重新激活到T1或T2表型。我们提出，在炎症性中枢神经系统疾病（如ms）中，PC可能参与了迁移穿过血脑屏障的白细胞的选择和极化。我们将研究它们在ag特异性TCR转基因小鼠中诱导原代效应细胞的作用，以及在引物动物中将记忆TO重新刺激为记忆效应细胞的作用。我们将探讨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.