Identification of proliferating dendritic cell precursors in mouse blood.

Identification of proliferating dendritic cell precursors in mouse blood.
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DOI:
10.1084/jem.175.5.1157
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发表时间:
1992-05-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Schuler G
Schuler G
中科院分区:
其他
文献类型:
--
作者:
Inaba K;Steinman RM;Pack MW;Aya H;Inaba M;Sudo T;Wolpe S;Schuler G

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虽然已知树突状细胞起源于原位增殖的前体,但很难在培养中识别祖细胞。我们发现,在补充了粒细胞/巨噬细胞集落刺激因子(GM-CSF)的小鼠血液培养中,生长的树突状细胞聚集发育,而不是其他csf。树突状细胞前体来源于ia阴性和非粘附部分。树突状细胞的聚集在培养1周左右出现,每10(6)个血液白细胞形成100或更多这样的簇。聚集体可以被移除并传代培养为扩展的簇,簇上覆盖着具有树突状细胞的活动片状过程(“面纱”)的细胞。约2周时,大量单一的、主要的组织相容性复合体(MHC)ⅱ类树突状细胞开始释放到培养基中。联合免疫过氧化物酶和[3H]胸腺嘧啶放射自显像显示,在聚集体内增殖的细胞缺乏成熟树突状细胞上发现的某些抗原标记物。然而,在脉冲追踪方案中,[3H]胸腺嘧啶标记的后代表现出许多典型的树突状细胞特征,包括丰富的MHC II类和单克隆抗体2A1鉴定的细胞质颗粒抗原。后代树突状细胞是混合白细胞反应的有效刺激物,注射到脚垫后可以回到淋巴结的t依赖区域。我们得出结论,小鼠血液中含有依赖于GM- csf的增殖祖细胞,这些祖细胞产生大量具有特征形态、移动性、表型和强T细胞刺激功能的树突状细胞。
While it has been known that dendritic cells arise from proliferating precursors in situ, it has been difficult to identify progenitors in culture. We find that aggregates of growing dendritic cells develop in cultures of mouse blood that are supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF) but not other CSFs. The dendritic cell precursor derives from the Ia-negative and nonadherent fraction. The aggregates of developing dendritic cells appear at about 1 wk of culture, with 100 or more such clusters being formed per 10(6) blood leukocytes. The aggregates can be dislodged and subcultured as expanding clusters that are covered with cells having the motile sheet-like processes ("veils") of dendritic cells. By about 2 wk, large numbers of single, major histocompatibility complex (MHC) class II-rich dendritic cells begin to be released into the medium. Combined immunoperoxidase and [3H]thymidine autoradiography show that the cells that proliferate within the aggregate lack certain antigenic markers that are found on mature dendritic cells. However, in pulse- chase protocols, the [3H]thymidine-labeled progeny exhibit many typical dendritic cell features, including abundant MHC class II and a cytoplasmic granular antigen identified by monoclonal antibody 2A1. The progeny dendritic cells are potent stimulators of the mixed leukocyte reaction and can home to the T-dependent areas of lymph node after injection into the footpads. We conclude that mouse blood contains GM- CSF-dependent, proliferating progenitors that give rise to large numbers of dendritic cells with characteristic morphology, mobility, phenotype, and strong T cell stimulatory function.