Rössner Susanne, Voigtländer Constanze, Wiethe Carsten, Hänig Jens, Seifarth Christian, Lutz Manfred B
Department of Dermatology, University Hospital Erlangen, Germany.
Eur J Immunol. 2005 Dec;35(12):3533-44. doi: 10.1002/eji.200526172.
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.
迄今为止，髓样树突状细胞（DC）的耐受性活性主要归因于未成熟或半成熟分化阶段，而从未归因于其前体细胞。尽管已在体外分离出髓样抑制细胞（MSC），但其与DC的发育关系及其精确表型仍不清楚。在此，我们描述了将MSC作为髓样DC前体的产生过程，其在体外对同种异体和OVA特异性CD4 +和CD8 + T细胞反应具有强大的抑制活性。这些MSC在低GM-CSF条件下8-10天后或在高GM-CSF条件下3-4天后短暂出现在骨髓（BM）细胞的DC培养物中。它们代表具有环形核的CD11c-髓样前体细胞，并且是Gr-1low（即Ly-6C +，Ly-6Glow），CD11b +，CD31 +，ER-MP58 +，去唾液酸GM1 +和F4/80 +。分选的MSC在6天内发育成CD11c + DC。它们的抑制活性部分取决于IFN-γ刺激。抑制作用是通过需要细胞接触和一氧化氮的机制介导的，但与TNF，CD1d和TGF-β无关。总之，我们的数据描述了在体外发育为未成熟DC之前具有独特抑制机制的MSC的产生过程。
