Abstract
Background:
Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4(+) T cell and NKT cell responses.
Methodology/principal findings:
Here we studied the role of the co-inhibitory molecule B7-H1 (PD-L1, CD274) on semi-mature DC that were generated from bone marrow (BM) cells of B7-H1(-/-) mice and applied to the model of Experimental Autoimmune Encephalomyelitis (EAE). Injections of B7-H1-deficient DC showed increased EAE protection as compared to wild type (WT)-DC. Injections of B7-H1(-/-) TNF-DC induced higher release of peptide-specific IL-10 and IL-13 after restimulation in vitro together with elevated serum cytokines IL-4 and IL-13 produced by NKT cells, and reduced IL-17 and IFN-gamma production in the CNS. Experiments in CD1d(-/-) and Jalpha281(-/-) mice as well as with type I and II NKT cell lines indicated that only type II NKT cells but not type I NKT cells (invariant NKT cells) could be stimulated by an endogenous CD1d-ligand on DC and were responsible for the increased serum cytokine production in the absence of B7-H1.
Conclusions/significance:
Together, our data indicate that BM-DC express an endogenous CD1d ligand and B7-H1 to ihibit type II but not type I NKT cells. In the absence of B7-H1 on these DC their tolerogenic potential to stimulate tolerogenic CD4(+) and NKT cell responses is enhanced.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD1d / immunology*
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Antigens, Surface / metabolism
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Apoptosis Regulatory Proteins / metabolism
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B7-1 Antigen / metabolism
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B7-H1 Antigen
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Biomarkers / metabolism
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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Cell Line
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Central Nervous System / drug effects
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Central Nervous System / immunology
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Central Nervous System / pathology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Epitopes / immunology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology*
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Membrane Glycoproteins / deficiency*
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Membrane Glycoproteins / metabolism
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Mice
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Natural Killer T-Cells / drug effects
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Natural Killer T-Cells / immunology*
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Natural Killer T-Cells / metabolism
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Organic Chemicals / immunology
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Peptides / deficiency*
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Peptides / metabolism
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Programmed Cell Death 1 Receptor
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Tumor Necrosis Factor-alpha / administration & dosage
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Antigens, CD1d
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Antigens, Surface
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Apoptosis Regulatory Proteins
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B7-1 Antigen
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B7-H1 Antigen
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Biomarkers
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Cd274 protein, mouse
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Epitopes
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Membrane Glycoproteins
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Organic Chemicals
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Pdcd1 protein, mouse
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Peptides
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Programmed Cell Death 1 Receptor
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Tolerogen
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Tumor Necrosis Factor-alpha