The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20070064
The Journal of Experimental Medicine, Vol. 204, No. 9, 2023-2030
The Rockefeller University Press, 0022-1007 $30.00
© Galea et al.
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Brief Definitive Report

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

Ian Galea1, Martine Bernardes-Silva1, Penny A. Forse1, Nico van Rooijen2, Roland S. Liblau3, and V. Hugh Perry1

1 CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton SO16 7PX, UK
2 Department of Molecular Cell Biology, Amsterdam 1007 MB, Netherlands
3 Institut National de la Sante et de la Recherche Medicale U563, Centre de Physiopathologie de Toulouse Purpan, Purpan Hospital, 31000 Toulouse, France

CORRESPONDENCE Ian Galea: I.Galea{at}soton.ac.uk

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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