The level of B7 homologue 1 expression on brain DC is decisive for CD8 Treg cell recruitment into the CNS during EAE.
DC in the CNS have emerged as the major rate-limiting factor for immune invasion and subsequent neuroinflammation during EAE. The mechanism of how this is regulated by brain-localized DC remains unknown. Here, we describe the ability of brain-localized DC expressing B7-H1 molecules to recruit CD8(+) T cells to the site of inflammation. Using intracerebral microinjections of B7-homologue 1-deficient DC, we demonstrate a substantial brain infiltration of CD8(+) T cells displaying a regulatory phenotype (CD122(+)) and function, resulting in a decrease of EAE peak clinical values. The recruitment of regulatory-type CD8(+) T cells into the CNS and the role of brain DC expressing B7-homologue 1 molecules in this process open up the possibility of DC-targeted therapeutic manipulation of neuroinflammatory diseases.
University of Wuerzburg, Department of Neurology, Wuerzburg, Germany.
Alla L
AL
Zozulya
Sonja
S
Ortler
Zsuzsanna
Z
Fabry
Matyas
M
Sandor
Heinz
H
Wiendl
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D049109:Cell Proliferation; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance / Q000502:physiology; D053646:Interleukin-2 Receptor beta Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D010455:Peptides / Q000378:metabolism*; D054399:Receptors, CCR6 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination / Q000379:methods
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498126:CCR6 protein, mouse; C498919:Cd274 protein, mouse; D006023:Glycoproteins; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D008562:Membrane Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010455:Peptides; D054399:Receptors, CCR6; C445081:myelin oligodendrocyte glycoprotein (35-55)