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.
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