Contrasting Effects of TGF‐β1 and TNF‐α on the Development of Dendritic Cells from Progenitors in Mouse Bone Marrow
Contrasting Effects of TGF‐β1 and TNF‐α on the Development of Dendritic Cells from Progenitors in Mouse Bone Marrow
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DOI：
10.1002/stem.150144
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发表时间：
1997-03
期刊：
影响因子：
5.2
通讯作者：
Y. Yamaguchi;H. Tsumura;M. Miwa;K. Inaba
中科院分区：
文献类型：
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作者：
Y. Yamaguchi;H. Tsumura;M. Miwa;K. Inaba
树突状细胞（DC）是白细胞和用于T细胞应答的特化抗原呈递细胞的独特群体。先前的工作表明，GM-CSF可以诱导小鼠骨髓中增殖祖细胞产生大量DC。我们已经监测了这些培养物中潜在的增强和抑制细胞因子的作用。在这个系统中，许多未成熟的DC在培养的前六天从增殖的前体发育而来，并且在第6 - 8天之间发生典型的非粘附和非复制DC的成熟。成熟伴随着主要组织相容性复合物II类（MHC II）和B7 - 2/CD 86的表达以及混合白细胞反应刺激活性的大幅增加。肿瘤坏死因子-α（TNF-α），以前被证明是人类DC发育所必需的，被发现在培养的最后两天增强小鼠DC的成熟。另一方面，转化生长因子-β1（TGF-β1）几乎完全阻断了DC的成熟，但必须在培养的前6天给予，此时DC正在积极增殖。TGF-β1不能阻断未成熟的、MHC II阳性但B7 - 2/CD 86阴性DC的产生。只要培养物中去除了携带Fc受体的细胞，或添加了TNF-α，则在第6 - 8天之间发生成熟。在这两种情况下，即使TGF-β1保留在培养物中，成熟也没有被阻断。我们的结论是，其他细胞因子可以改变DC对GM-CSF的反应。TGF-β1是抑制性的，但仅间接通过携带Fc受体的抑制性细胞，推测为抑制性巨噬细胞，而TNF-α增强DC的最终成熟。
Dendritic cells (DC) are a distinct population of leukocytes and specialized antigen‐presenting cells for T cell responses. Prior work has shown that GM‐CSF can induce the development of large numbers of DC from proliferating progenitors in mouse bone marrow. We have monitored the effects of potentially enhancing and suppressive cytokines in these cultures. In this system, many immature DC develop from proliferating precursors during the first six days of culture, and between days 6‐8 maturation of typical nonadherent and nonreplicating DC takes place. The maturation is accompanied by a large increase in the expression of major histocompatibilities complex class II (MHC II) and B7‐2/CD86, and in mixed leukocyte reaction stimulating activity. Tumor necrosis factor‐α (TNF‐α), previously shown to be required for development of human DC, was found to enhance the maturation of mouse DC in the last two days of culture. Transforming growth factor‐β1(TGF‐β1), on the other hand, almost totally blocked DC maturation, but it had to be given in the first six days of culture when the DC were actively proliferating. TGF‐β1 did not block the production of immature, MHC II‐positive but B7‐2/CD86‐negative DC. Maturation would take place between days 6‐8 as long as the cultures were depleted of Fc‐receptor‐bearing cells, or if TNF‐α were added. In both instances, maturation was not blocked even when TGF‐β1 remained in the culture. We conclude that the development of DC, in response to GM‐CSF, can be modified by other cytokines. TGF‐β1 is suppressive but only indirectly via Fc‐receptor‐bearing suppressive cells, presumably suppressive macrophages, while TNF‐α enhances the final maturation of DC.