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

An antigen-specific pathway for CD8 T cells across the blood-brain barrier
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 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.
0022-1007
2023-2030
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Bernardes-Silva, Martine
513d0bcc-f15d-44d6-9373-a0d78b2b2e07
Forse, Penny A.
f4f114bc-6184-44d5-ac7e-6e792e8fd1dd
van Rooijen, Nico
a9f3fc94-192d-4e2d-b662-765bd778bc55
Liblau, Roland S.
ee2479e2-8dff-42a5-b1ef-de04fc3e4acf
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Bernardes-Silva, Martine
513d0bcc-f15d-44d6-9373-a0d78b2b2e07
Forse, Penny A.
f4f114bc-6184-44d5-ac7e-6e792e8fd1dd
van Rooijen, Nico
a9f3fc94-192d-4e2d-b662-765bd778bc55
Liblau, Roland S.
ee2479e2-8dff-42a5-b1ef-de04fc3e4acf
Perry, V. Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4

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. The Journal of Experimental Medicine, 204 (9), 2023-2030. (doi:10.1084/jem.20070064).

Record type: Article

Abstract

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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Submitted date: 5 January 2007
Published date: 3 September 2007

Identifiers

Local EPrints ID: 56802
URI: http://eprints.soton.ac.uk/id/eprint/56802
ISSN: 0022-1007
PURE UUID: ddf1794d-b9b4-4782-a243-9d01369578b7
ORCID for Ian Galea: ORCID iD orcid.org/0000-0002-1268-5102

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Date deposited: 11 Aug 2008
Last modified: 10 Dec 2019 01:46

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