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Publication : Myeloid dendritic cell precursors generated from bone marrow suppress T cell responses via cell contact and nitric oxide production in vitro.

First Author  Rössner S Year  2005
Journal  Eur J Immunol Volume  35
Issue  12 Pages  3533-44
PubMed ID  16331707 Mgi Jnum  J:113738
Mgi Id  MGI:3687597 Doi  10.1002/eji.200526172
Citation  Rossner S, et al. (2005) Myeloid dendritic cell precursors generated from bone marrow suppress T cell responses via cell contact and nitric oxide production in vitro. Eur J Immunol 35(12):3533-44
abstractText  Tolerogenic activity of myeloid dendritic cells (DC) has so far been attributed mostly to immature or semi-mature differentiation stages but never to their precursor cells. Although myeloid suppressor cells (MSC) have been isolated ex vivo, their developmental relationship to DC and their precise phenotype remained elusive. Here, we describe the generation of MSC as myeloid DC precursors with potent suppressive activity on allogeneic and OVA-specific CD4+ and CD8+ T cell responses in vitro. These MSC appear transiently in DC cultures of bone marrow (BM) cells after 8-10 days under low GM-CSF conditions or after 3-4 days under high GM-CSF conditions. They represent CD11c- myeloid precursor cells with ring-shaped nuclei and are Gr-1low (i.e. Ly-6C+, Ly-6Glow), CD11b+, CD31+, ER-MP58+, asialoGM1+ and F4/80+. Sorted MSC develop into CD11c+ DC within 6 days. Their suppressor activity partially depends on IFN-gamma stimulation. Suppression is mediated through mechanisms requiring cell contact and nitric oxide but is independent of TNF, CD1d and TGF-beta. Together, our data describe the generation of MSC with distinct suppressor mechanisms in vitro preceding their development into immature DC.
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