Characterization of epithelial V-like antigen in human choroid plexus epithelial cells: Potential role in CNS immune surveillance

Abstract

Prior work demonstrated that immune surveillance of the brain occurs primarily through the blood-cerebrospinal (CSF) fluid barrier rather than the blood-brain barrier endothelium. Recently, we identified epithelial V-like antigen (EVA), an immunoglobulin-like adhesion molecule, as a regulator of blood-CSF barrier integrity in a mouse model. Here we characterized EVA expression and function in human choroid plexus epithelial cells and analyzed its role in CD4 T lymphocyte adhesion. In human choroid plexus epithelial cells and a subset of CD4 T lymphocytes, EVA is expressed at high levels. Epithelial adhesion of T lymphocytes is inhibited by a blocking monoclonal antibody that recognizes EVA. T cell adhesion elicits calcium flux in choroid plexus epithelial cells that also can be blocked by an EVA-specific antibody. EVA-positive cell–cell contacts between epithelial and T cells are associated with increased complexity of cytoskeletal epithelial morphology. These results demonstrate that EVA is expressed in human choroid plexus epithelial cells and CD4 T lymphocytes and regulates CD4+ T lymphocyte adhesion to human choroid plexus epithelial cells in vitro. These data suggest a novel mechanism to regulate CNS immune surveillance.