An antigen-specific pathway for CD8 T cells across the blood-brain barrier
Galea, Ian, Bernardes-Silva, Martine, Forse, Penny A., van Rooijen, Nico, Liblau, Roland S. and Perry, V. Hugh (2007) An antigen-specific pathway for CD8 T cells across the blood-brain barrier. Journal of Experimental Medicine, 204, (9), 2023-2030. (doi:10.1084/jem.20070064).
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CD8 T cells are nature's foremost defense in encephalitis and brain tumors. Antigen-specific CD8 T cells need to enter the brain to exert their beneficial effects. On the other hand, traffic of CD8 T cells specific for neural antigen may trigger autoimmune diseases like multiple sclerosis. T cell traffic into the central nervous system is thought to occur when activated T cells cross the blood-brain barrier (BBB) regardless of their antigen specificity, but studies have focused on CD4 T cells. Here, we show that selective traffic of antigen-specific CD8 T cells into the brain occurs in vivo and is dependent on luminal expression of major histocompatibility complex (MHC) class I by cerebral endothelium. After intracerebral antigen injection, using a minimally invasive technique, transgenic CD8 T cells only infiltrated the brain when and where their cognate antigen was present. This was independent of antigen presentation by perivascular macrophages. Marked reduction of antigen-specific CD8 T cell infiltration was observed after intravenous injection of blocking anti–MHC class I antibody. These results expose a hitherto unappreciated route by which CD8 T cells home onto their cognate antigen behind the BBB: luminal MHC class I antigen presentation by cerebral endothelium to circulating CD8 T cells. This has implications for a variety of diseases in which antigen-specific CD8 T cell traffic into the brain is a beneficial or deleterious feature.
|Subjects:||R Medicine > RB Pathology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Q Science > QR Microbiology > QR180 Immunology
|Divisions:||University Structure - Pre August 2011 > School of Biological Sciences
University Structure - Pre August 2011 > School of Medicine
|Date Deposited:||11 Aug 2008|
|Last Modified:||12 May 2013 01:19|
|Contributors:||Galea, Ian (Author)
Bernardes-Silva, Martine (Author)
Forse, Penny A. (Author)
van Rooijen, Nico (Author)
Liblau, Roland S. (Author)
Perry, V. Hugh (Author)
|Date:||3 September 2007|
|Contact Email Address:||I.Galea@soton.ac.uk|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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