Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B7-1 Antigen / metabolism*
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B7-H1 Antigen
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Brain / cytology
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Brain / immunology
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Brain / pathology
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Movement / immunology*
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Cell Proliferation
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Central Nervous System / immunology*
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Central Nervous System / pathology
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Dendritic Cells / transplantation
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Encephalomyelitis, Autoimmune, Experimental / diagnosis
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Female
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Glycoproteins / administration & dosage
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Glycoproteins / immunology
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Immune Tolerance / physiology
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Interleukin-2 Receptor beta Subunit / metabolism
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Peptides / metabolism*
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Receptors, CCR6 / metabolism
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Spleen / cytology
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Spleen / immunology
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
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Vaccination / methods
Substances
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B7-1 Antigen
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B7-H1 Antigen
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CCR6 protein, mouse
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Cd274 protein, mouse
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Glycoproteins
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Il2rb protein, mouse
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Interleukin-2 Receptor beta Subunit
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Membrane Glycoproteins
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Peptides
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Receptors, CCR6
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myelin oligodendrocyte glycoprotein (35-55)