TOKITA Daisuke
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position |
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Article types | Original article |
Language | English |
Peer review | Peer reviewed |
Title | Allostimulatory activity of bone marrow-derived plasmacytoid dendritic cells is independent of indoleamine dioxygenase but regulated by inducible costimulator ligand expression. |
Journal | Formal name:Human immunology Abbreviation:Hum Immunol ISSN code:18791166/01988859 |
Domestic / Foregin | Foregin |
Volume, Issue, Page | 70(5),pp.313-20 |
Author and coauthor | Colvin Bridget L, Sumpter Tina L, Tokita Daisuke, Salati Jennifer, Mellor Andrew L, Thomson Angus W |
Publication date | 2009/05 |
Summary | We investigated the role of two key immunoregulatory molecules, indoleamine dioxygenase (IDO) and inducible costimulator ligand (ICOSL), in determining the function of bone marrow (BM)-derived plasmacytoid (p)DC, which offer the potential for therapy of allograft rejection. pDC generated from BM of wild-type (WT) or IDO knockout (KO) C57BL/6 mice were used to stimulate T-cell proliferation and interferon-gamma (IFN-gamma) production in response to alloantigen (alloAg) via the direct or indirect pathways. In some experiments, pDC were first activated by exposure to CpG +/- CTLA4Ig for IDO induction via B7 ligation. Although IDO KO pDC induced enhanced T-cell responses compared with WT pDC, the use of the IDO inhibitor 1-methyltryptophan (1-MT) demonstrated that the inferior stimulatory capacity of WT pDC was not caused by the production of functional IDO, even under IDO-inducing conditions. The DNAX-activating protein of 12 kDa (DAP12), which inhibits functional IDO expression, was expressed in BM-pDC. DAP12 silencing increased the T-cell stimulatory capacity of WT pDC, but only in the presence of 1-MT. Compared with WT pDC, activated IDO KO DC expressed much lower levels of ICOSL. Moreover, when ICOSL was blocked on WT pDC, T-cell proliferation resembled that induced by IDO KO pDC, and interleukin (IL)-10 secretion in MLR was markedly decreased. These findings implicate ICOSL-induced IL-10, but not IDO in the regulation of BM-derived pDC function. |
DOI | 10.1016/j.humimm.2009.01.021 |
PMID | 19208362 |