GRANULOCYTES, MACROPHAGES, AND DENDRITIC CELLS ARISE FROM A COMMON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-NEGATIVE PROGENITOR IN MOUSE BONE-MARROW

GRANULOCYTES, MACROPHAGES, AND DENDRITIC CELLS ARISE FROM A COMMON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-NEGATIVE PROGENITOR IN MOUSE BONE-MARROW
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DOI:
10.1073/pnas.90.7.3038
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发表时间:
1993-04-01
影响因子:
11.1
通讯作者:
STEINMAN, RM
STEINMAN, RM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
INABA, K;INABA, M;STEINMAN, RM

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树突状细胞的发育起源是一种主要的组织相容性复合物(MHC)II类富含抗原抗原的细胞的专业系统,可用于T细胞免疫和耐受性,但没有很好地表征。已知粒细胞巨噬细胞刺激因子(GM-CSF)刺激树突状细胞,包括小鼠骨髓悬浮培养物中MHC II类阴性前体的生长和发育。在这里,我们研究了半固体甲基纤维素培养物中的菌落形成,这是一种经典的生物测定系统,其中GM-CSF诱导了混合粒细胞 - 巨噬细胞菌落的形成。当从MHC II类阴性前体诱导菌落时,一小部分(1-2%)的典型树突状细胞与巨噬细胞和粒细胞一起发展。树突状细胞以其细胞学特征,高水平的MHC II类产品和不同细胞内颗粒抗原的区分。通过使用对塑料的差异依从性,从菌落中分离出各种髓样细胞类型的富集群体。只有树突状细胞刺激原发性T细胞免疫反应,混合的白细胞反应,并且效力与从脾脏分离的典型树突状细胞相当。来自混合或纯菌落的巨噬细胞作为刺激细胞无活性。因此,髓样发育粒细胞,巨噬细胞和树突状细胞can的三个不同途径是由GM-CSF誓章下的常见MHC II类阴性祖细胞发展而来的。
The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development-granulocytes, macrophages, and dendritic cells-can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF.