Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow.
Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow.
复制标题
DOI：
10.4049/jimmunol.149.8.2681
复制
发表时间：
1992-10
影响因子：
4.4
通讯作者：
C. Reid;A. Stackpoole;A. Meager;J. Tikerpae
中科院分区：
文献类型：
--
作者：
C. Reid;A. Stackpoole;A. Meager;J. Tikerpae
在半固体培养基中的人骨髓培养物中观察到具有朗格汉斯细胞功能和部分结构属性的 CD1a+ HLA-DR+/DQ+ CD4+ 细胞集落，并被认为是早期祖细胞树突状/朗格汉斯细胞 CFU (CFU-DL) 的后代。使用化学成分确定的无血清系统来培养未分级和高度富集的骨髓祖细胞群，研究了这些细胞的细胞因子调节生长。尽管在含有 PHA 刺激的白细胞条件培养基 (PHA-LCM) 的血清培养物中，未分级细胞生长是最佳的，但即使在不存在 PHA-LCM 的情况下，在血清中也观察到 CFU-DL 的增殖不理想。当粒细胞-巨噬细胞 CSF (GM-CSF)、IL-3、粒细胞 CSF (G-CSF) 和巨噬细胞 CSF (M-CSF) 存在于粒细胞集落形成单位 (CFU-G) 和巨噬细胞集落形成单位 (CFU-M) 生长的最佳水平时，在无血清条件下未观察到集落。将IL-1α添加到这些细胞因子中刺激了少量的CFU-DL。然而，在存在 GM-CSF 和 IL-3 的情况下，TNF-α 或 TNF-β (5 U/ml) 都能够非常有效地促进生长高达最佳生长的 82%，并且在这些浓度下 CFU-G 的生长也得到增强。 TNF 仅在培养的前 3 天有活性，较高浓度的 TNF-α（而非 TNF-β）对 CFU-DL 和 CFU-G 均具有抑制作用。富含 CD34+ 细胞的群体的骨髓祖细胞 (CFU-G + CFU-M) 和 CFU-DL 也分别富集至 36 倍和 48 倍，并且 CD34+ 细胞的单细胞培养物产生含有 CD1a+ 树突状细胞和 CD1a- 巨噬细胞的单集落。因此，骨髓中的树突状/朗格汉斯祖细胞表达CD34，具有巨噬细胞和树突状细胞分化的能力，并且依赖于造血生长因子和TNF来在体外进一步发育。
Colonies of CD1a+ HLA-DR+/DQ+ CD4+ cells with the functional and some of the structural attributes of Langerhans cells are observed in human bone marrow cultures in semi-solid media and are assumed to be the progeny of an early progenitor, the dendritic/Langerhans cell CFU (CFU-DL). The cytokine-regulated growth of these cells has been studied using a chemically defined serum-free system to culture both unfractionated and highly enriched bone marrow progenitor cell populations. Although unfractionated cell growth was optimal in serum replete cultures with PHA-stimulated leukocyte-conditioned medium (PHA-LCM) suboptimal proliferation of CFU-DL was observed in serum even in the absence of PHA-LCM. No colonies were observed under serum-free conditions when granulocyte-macrophage CSF (GM-CSF), IL-3, granulocyte CSF (G-CSF), and macrophage CSF (M-CSF) were present at levels optimal for granulocyte colony-forming unit (CFU-G) and macrophage colony-forming unit (CFU-M) growth. Addition of IL-1 alpha to these cytokines stimulated a small number of CFU-DL. However, in the presence of GM-CSF and IL-3, TNF-alpha or TNF-beta (5 U/ml) were both highly effective in promoting growth up to 82% of optimal and CFU-G growth was also enhanced at these concentrations. TNF was only active during the first 3 days of culture and higher concentrations of TNF-alpha but not TNF-beta were inhibitory for both CFU-DL and CFU-G. CD34+ cell-enriched populations were also enriched for both myeloid progenitors (CFU-G + CFU-M) and CFU-DL to 36- and 48-fold, respectively, and single cell cultures of CD34+ cells yielded single colonies containing both CD1a+ dendritic cells and CD1a- macrophages. Thus dendritic/Langerhans progenitors in the bone marrow expresses CD34, have a capacity for both macrophage and dendritic cell differentiation, and depend on hemopoietic growth factors and TNF for their further development in vitro.