| First Author | Brandl C | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 5 | Pages | e10800 |
| PubMed ID | 20520738 | Mgi Jnum | J:160903 |
| Mgi Id | MGI:4456293 | Doi | 10.1371/journal.pone.0010800 |
| Citation | Brandl C, et al. (2010) B7-H1-deficiency enhances the potential of tolerogenic dendritic cells by activating CD1d-restricted type II NKT cells. PLoS One 5(5):e10800 |
| abstractText | 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. |
