B7-H1-deficiency enhances the potential of tolerogenic dendritic cells by activating CD1d-restricted type II NKT cells.
BACKGROUND
Dendritic cells (DC) can act tolerogenic at a semi-mature stage by induction of protective CD4(+) T cell and NKT cell responses.


RESULTS
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
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.
Institute of Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
Carolin
C
Brandl
Sonja
S
Ortler
Thomas
T
Herrmann
Susanna
S
Cardell
Manfred B
MB
Lutz
Heinz
H
Wiendl
D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology*; D000954:Antigens, Surface / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D060890:B7-H1 Antigen; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D055611:Natural Killer T-Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009930:Organic Chemicals / Q000276:immunology; D010455:Peptides / Q000172:deficiency* / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology
D055610:Antigens, CD1d; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; C498919:Cd274 protein, mouse; D000939:Epitopes; D008562:Membrane Glycoproteins; D009930:Organic Chemicals; C491383:Pdcd1 protein, mouse; D010455:Peptides; D061026:Programmed Cell Death 1 Receptor; C029248:Tolerogen; D014409:Tumor Necrosis Factor-alpha