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An antigen-specific pathway for CD8 T cells across the blood-brain barrier

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 ce...

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Detalles Bibliográficos
Autores principales: Galea, Ian, Bernardes-Silva, Martine, Forse, Penny A., van Rooijen, Nico, Liblau, Roland S., Perry, V. Hugh
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118703/
https://www.ncbi.nlm.nih.gov/pubmed/17682068
http://dx.doi.org/10.1084/jem.20070064
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author Galea, Ian
Bernardes-Silva, Martine
Forse, Penny A.
van Rooijen, Nico
Liblau, Roland S.
Perry, V. Hugh
author_facet Galea, Ian
Bernardes-Silva, Martine
Forse, Penny A.
van Rooijen, Nico
Liblau, Roland S.
Perry, V. Hugh
author_sort Galea, Ian
collection PubMed
description 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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spelling pubmed-21187032008-03-03 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. Perry, V. Hugh J Exp Med Brief Definitive Reports 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. The Rockefeller University Press 2007-09-03 /pmc/articles/PMC2118703/ /pubmed/17682068 http://dx.doi.org/10.1084/jem.20070064 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Galea, Ian
Bernardes-Silva, Martine
Forse, Penny A.
van Rooijen, Nico
Liblau, Roland S.
Perry, V. Hugh
An antigen-specific pathway for CD8 T cells across the blood-brain barrier
title An antigen-specific pathway for CD8 T cells across the blood-brain barrier
title_full An antigen-specific pathway for CD8 T cells across the blood-brain barrier
title_fullStr An antigen-specific pathway for CD8 T cells across the blood-brain barrier
title_full_unstemmed An antigen-specific pathway for CD8 T cells across the blood-brain barrier
title_short An antigen-specific pathway for CD8 T cells across the blood-brain barrier
title_sort antigen-specific pathway for cd8 t cells across the blood-brain barrier
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118703/
https://www.ncbi.nlm.nih.gov/pubmed/17682068
http://dx.doi.org/10.1084/jem.20070064
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