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

Department of Neurology and Program in Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
Neuroscience Letters (Impact Factor: 2.03). 03/2011; 495(2):115-20. DOI: 10.1016/j.neulet.2011.03.051
Source: PubMed


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.

10 Reads
  • Source
    • "Another difference is that kolmer cells are only present in the adult CP (Strazielle and Ghersi-Egea, 2000). Given the immunologic complexity of the stroma, much of the cell diversity is driven by immunologic insult, or CNS injury (Mitchell et al., 2009; Wojcik et al., 2011; Hasegawa-Ishii et al., 2013; Shechter et al., 2013; Szmydynger-Chodobska et al., 2013). Previous analysis in zebrafish failed to demonstrate presence of unlabelled cells in the mCP of transgenics suggesting that all cell lineages except vasculature derive from GFP-positive cells (Garcia-Lecea et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The blood-cerebrospinal fluid boundary is present at the level of epithelial cells of the choroid plexus. As one of the sources of the cerebrospinal fluid (CSF), the choroid plexus (CP) plays an important role during brain development and function. Its formation has been studied largely in mammalian species. Lately, progress in other model animals, in particular the zebrafish, has brought a deeper understanding of CP formation, due in part to the ability to observe CP development in vivo. At the same time, advances in comparative genomics began providing information, which opens a possibility to understand further the molecular mechanisms involved in evolution of the CP and the blood-cerebrospinal fluid boundary formation. Hence this review focuses on analysis of the CP from developmental and evolutionary perspectives.
    Frontiers in Neuroscience 11/2014; 8:363. DOI:10.3389/fnins.2014.00363 · 3.66 Impact Factor
  • Source
    • "Cells should be left undisturbed for at least 16 hours, then Epithelial Cell Medium supplemented with 10% FCS, antibiotics, epidermal growth factor and insulin should be added; all of these reagents are available from the supplier of this cell line. However, in some studies, these cells were grown successfully in the medium that included 2% FCS [30]. When cells attach they display polygonal shaped sheets of neighboring cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of human choroid plexus (CP) epithelium in the transport of solutes between the blood and the cerebrospinal fluid and/or in secretion processes may be studied by employing several experimental approaches. There are a number of in vitro techniques for human CP epithelium (CPE) and all have limitations that do not exclude them a priori, but that should be carefully taken into consideration. Developmental and morphological studies have been largely performed on human choroid plexus samples of either embryonic or post-mortem origin. Functional uptake studies may be performed on pathologically unaltered CP samples obtained during surgical removal of choroid plexus tumors. This approach can be used to explore transport processes mainly across the apical side of the CPE, but cannot be used to study vectorial transport across the CPE. Also, these samples have limited viability. A monolayer of CPE in culture, grown on permeable supports, provides the best available tool to study transport processes or polarized secretion by the CP, but thus far only limited attempts to culture these cells have been published and they mainly include data from neoplastic CPE. A study that used a human papilloma-derived cell line in culture showed that it forms a monolayer with barrier properties, although the cells express pleomorphic and neoplastic features and lack contact inhibition. Other cell cultures express some CPE markers but do not develop tight junctions/barrier properties. This article reviews the main characteristics and limitations of available in vitro methods to study human CPE, which could help researchers choose an appropriate experimental approach for a particular study.
    Fluids and Barriers of the CNS 02/2013; 10(1):10. DOI:10.1186/2045-8118-10-10
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The CNS, which consists of the brain and spinal cord, is continuously monitored by resident microglia and blood-borne immune cells such as macrophages, dendritic cells and T cells to detect for damaging agents that would disrupt homeostasis and optimal functioning of these vital organs. Further, the CNS must balance between vigilantly detecting for potentially harmful factors and resolving any immunological responses that in themselves can create damage if left unabated. We discuss the physiological roles of the immune sentinels that patrol the CNS, the molecular markers that underlie their surveillance duties, and the consequences of interrupting their functions following injury and infection by viruses such as JC virus, human immunodeficiency virus, herpes simplex virus and West Nile virus.
    Nature Neuroscience 07/2012; 15(8):1096-101. DOI:10.1038/nn.3161 · 16.10 Impact Factor
Show more


10 Reads
Available from