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Rapid up regulation of CNS VEGF is initiated by CD8 T cells in a murine model of BBB disruption
Author(s) -
Johnson Aaron Jon,
Suidan Georgette L,
Chen Yi,
Pirko Istvan
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1072.4
Subject(s) - occludin , tight junction , vascular permeability , cd8 , cytotoxic t cell , astrocyte , blood–brain barrier , microbiology and biotechnology , immunology , in vivo , biology , downregulation and upregulation , central nervous system , chemistry , antigen , cancer research , in vitro , neuroscience , endocrinology , biochemistry , gene
The role of inflammatory cells in promoting opening of the blood brain barrier (BBB) in neurological disease remains poorly understood. We have created a novel in vivo system to study BBB disruption using the Theilers murine encephalomyelitus virus (TMEV) model of multiple sclerosis. During acute TMEV infection, 70% of CNS infiltrating CD8 T cells are specific for a TMEV peptide, VP2 121–130, presented in the context of the Db Class I molecule. Intravenous injection of the VP2 121–130 peptide during the peak of CD8 T cell expansion in the CNS results in fatal vascular permeability characterized by: 1.) Astrocyte activation as detected by GFAP expression, 2.) Alteration of BBB tight junction proteins Z0‐2, Occludin and Claudin 5, 3.) Vascular permeability as measured by quantifiable T1 weighted MRI, and 4.) Severe motor deficit. Prior to these overt changes in CNS vascular permeability we observe high levels of active VEGF protein upregulated in the CNS implying an important role for this factor in CNS vascular permeability. To our knowledge, this is the first demonstration of an antigen specific T cell response initiating the expression of VEGF in the CNS during a vascular permeability syndrome.