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.
CNS Inflammation Group, School of Biological Sciences, University of Southampton, Southampton, UK. I.Galea@soton.ac.uk
Ian
I
Galea
Martine
M
Bernardes-Silva
Penny A
PA
Forse
Nico
N
van Rooijen
Roland S
RS
Liblau
V Hugh
VH
Perry
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D000939:Epitopes / Q000187:drug effects / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018448:Models, Immunological
D000906:Antibodies; D000939:Epitopes; D015395:Histocompatibility Antigens Class I