Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor.
Dendritic cell development in culture from thymic precursor cells in the absence of granulocyte/macrophage colony-stimulating factor.
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DOI：
10.1084/jem.184.6.2185
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发表时间：
1996-12-01
期刊：
影响因子：
--
通讯作者：
Shortman K
中科院分区：
文献类型：
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作者：
Saunders D;Lucas K;Ismaili J;Wu L;Maraskovsky E;Dunn A;Shortman K
成年小鼠胸腺中最早的淋巴前体种群不仅显示出T细胞，而且在这项研究中转移到受辐射的受体中，也会培养这些分离的胸腺前体和细胞因子的混合物。诱导它们增殖并区分DC，但至少有70％的单个前体具有形成DC的能力。在混合白细胞培养物中T细胞刺激的功能性测试中作为正常的胸腺直流有效。然而，成熟的直流。从这些胸腺前体开发DC所需的七个细胞因子不包括粒细胞/巨噬细胞刺激因子（GM-CSF），通常是培养中DC发育所必需的。 CSF缺陷小鼠并没有阻止DC的发展。 GM-CSF的刺激在不存在的情况下，通过添加FLT3/FLK2配体增强了DC的发展，这与该细胞因子在体内的影响一致。 DC的谱系，可能是淋巴前体的起源，可能独立于髓样马内GM-CSF。
The earliest lymphoid precursor population in the adult mouse thymus had previously been shown to produce not only T cells, but also dendritic cell (DC) progeny on transfer to irradiated recipients. In this study, culture of these isolated thymic precursors with a mixture of cytokines induced them to proliferate and to differentiate to DC, but not to T lineage cells. At least 70% of the individual precursors had the capacity to form DC. The resultant DC were as effective as normal thymic DC in the functional test of T cell stimulation in mixed leukocyte cultures. The cultured DC also expressed high levels of class I and class II major histocompatibility complex, together with CD11c, DEC-205, CD80, and CD86, markers characteristic of mature DC in general. However, they did not express CD8α or BP-1, markers characteristic of normal thymic DC. The optimized mixture of five to seven cytokines required for DC development from these thymic precursors did not include granulocyte/macrophage colony stimulating factor (GM-CSF), usually required for DC development in culture. The addition of anti–GM-CSF antibody or the use of precursors from GM-CSF–deficient mice did not prevent DC development. Addition of GM-CSF was without effect on DC yield when interleukin (IL) 3 and IL-7 were present, although some stimulation by GM-CSF was noted in their absence. In contrast, DC development was enhanced by addition of the Flt3/Flk2 ligand, in line with the effects of the administration of this cytokine in vivo. The results indicate that the development of a particular lineage of DC, probably those of lymphoid precursor origin, may be independent of the myeloid hormone GM-CSF.