Neuroscience Letters 495 (2011) 115–120
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Characterization of epithelial V-like antigen in human choroid plexus epithelial
cells: Potential role in CNS immune surveillance
Elise Wojcika, Lisette M. Carrithersa, Michael D. Carrithersa,b,∗
aDepartment of Neurology and Program in Cellular and Molecular Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
bNeurology Service, William Middleton VA Hospital, Madison, WI 53705, USA
a r t i c l ei n f o
Received 11 February 2011
Received in revised form 16 March 2011
Accepted 17 March 2011
Blood-cerebrospinal fluid barrier
CD4 T lymphocyte
a b s t r a c t
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
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.
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
© 2011 Elsevier Ireland Ltd. All rights reserved.
The neuroprotective barriers include the blood brain barrier (BBB),
which is formed by tight junctions between brain endothelial cells,
and the blood-cerebrospinal fluid (CSF) barrier, which is regu-
lated by epithelial cells within the choroid plexus. T lymphocyte
trafficking across these barriers occurs in health in addition to
inflammatory disease states . Our prior work in mouse in vivo
models of immune cell trafficking demonstrated that immune
the blood-CSF barrier  and is partly mediated by the adhesion
molecule P selectin expressed on the choroid plexus epithelium
. Human memory T lymphocytes likely utilize the same path-
way to enter the cerebrospinal fluid . This pathway protects
the individual from developing infections of the central nervous
system (CNS) but also may lead to the initiation of new inflam-
matory lesions in patients with multiple sclerosis as suggested by
work in animal models [8,14].
Recently, our laboratory demonstrated that reduced lym-
phocyte immune surveillance in lymphocyte-deficient mice is
associated with increased blood-CSF barrier permeability. Based
on that observation, we analyzed CSF-barrier function and global
gene expression in immune-competent and lymphocyte-deficient
∗Corresponding author at: 1300 University Avenue, Room 2679, Madison, WI
53706, USA. Tel.: +1 608 265 8596; fax: +1 608 265 3170.
E-mail address: email@example.com (M.D. Carrithers).
for T lymphocyte CNS entry . These data revealed differential
expression of epithelial V-like antigen (EVA), a member of the
immunoglobulin superfamily of proteins , by choroid plexus
epithelial cells. Decreased expression of EVA in the choroid plexus
of lymphocyte-deficient mice is associated with increased per-
meability of the blood-CSF barrier, reduced cadherin expression
at epithelial cell contacts, and a less ordered morphology of the
Based on those results, we hypothesized that EVA regulates
permeability of the choroid plexus. Additional work from another
may mediate T lymphocyte adhesion to mouse thymic epithelial
cells . Here our goals were to characterize EVA expression in
human choroid plexus epithelial cells and analyze its role in CD4 T
lymphocyte adhesion. Our results suggest that EVA is expressed on
both human choroid plexus epithelial cells and a unique subset of
the two cell types.
Human choroid plexus epithelial cells were obtained from Sci-
enCell and grown according to the supplier’s recommendations in
Epithelial Cell Media (ECM) supplemented with 2% FBS, epidermal
cells at ScienCell and used from cell passages 1–4 in our labora-
0304-3940/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved.
E. Wojcik et al. / Neuroscience Letters 495 (2011) 115–120
(RG-3888) and the University of Wisconsin.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.neulet.2011.03.051.
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