Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782141088137478144 |
---|---|
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. |
format | Text |
id | pubmed-2118703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT galeaian anantigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT bernardessilvamartine anantigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT forsepennya anantigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT vanrooijennico anantigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT liblaurolands anantigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT perryvhugh anantigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT galeaian antigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT bernardessilvamartine antigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT forsepennya antigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT vanrooijennico antigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT liblaurolands antigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier AT perryvhugh antigenspecificpathwayforcd8tcellsacrossthebloodbrainbarrier |