Modulation of T cell-endothelial adhesion by astrocyte conditioned medium

Astrocytes and derived factors maintain the morphologic, phenotypic, and physiological properties of the blood-brain barrier. Astroglial cells may also modulate endothelial cell properties associated with the entry of inflammatory cells into the brain. The study of mechanisms of lymphocyte migration through the blood-brain barrier is critical to understanding the pathophysiology of autoimmune (multiple sclerosis) and virus-induced central nervous system diseases (HIV-induced dementia). In this context the contribution of astrocyte derived factors in regulating the interactions between inflammatory cells and endothelial cells of the blood-brain barrier was studied. The treatment of endothelial cells derived from brain or peripheral sources (hepatic) with astrocyte conditioned medium resulted in a dose dependent enhancement of adhesion of T cells to endothelium. The antigen specificity of the T cells did not influence the findings. Identical results were obtained with fresh Concanavalin A activated T cells and T cell hybridomas generated using myelin basic protein or chicken ovalbumin as immunogens. Further studies are in progress to define the active components in astrocyte conditioned medium and endothelial cell adhesion molecules that are regulated in order to gain a better understanding of mechanisms of inflammatory cell entry into the central nervous system.