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.
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3 September 2007
Brief Definitive Report|
August 06 2007
An antigen-specific pathway for CD8 T cells across the blood-brain barrier
Ian Galea,
Ian Galea
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
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Martine Bernardes-Silva,
Martine Bernardes-Silva
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
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Penny A. Forse,
Penny A. Forse
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
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Nico van Rooijen,
Nico van Rooijen
2Department of Molecular Cell Biology, Amsterdam 1007 MB, Netherlands
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Roland S. Liblau,
Roland S. Liblau
3Institut National de la Sante et de la Recherche Medicale U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France
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V. Hugh Perry
V. Hugh Perry
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
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Ian Galea
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
Martine Bernardes-Silva
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
Penny A. Forse
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
Nico van Rooijen
2Department of Molecular Cell Biology, Amsterdam 1007 MB, Netherlands
Roland S. Liblau
3Institut National de la Sante et de la Recherche Medicale U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France
V. Hugh Perry
1CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
CORRESPONDENCE Ian Galea: [email protected]
Received:
January 05 2007
Accepted:
June 28 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (9): 2023–2030.
Article history
Received:
January 05 2007
Accepted:
June 28 2007
Citation
Ian Galea, Martine Bernardes-Silva, Penny A. Forse, Nico van Rooijen, Roland S. Liblau, V. Hugh Perry; An antigen-specific pathway for CD8 T cells across the blood-brain barrier . J Exp Med 3 September 2007; 204 (9): 2023–2030. doi: https://doi.org/10.1084/jem.20070064
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