Reid C D, Stackpoole A, Meager A, Tikerpae J
Department of Haematology, Northwick Park Hospital and Clinical Research Centre, Harrow, Middlesex, United Kingdom.
J Immunol. 1992 Oct 15;149(8):2681-8.
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.
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一些结构特征的CD1a + HLA - DR + / DQ + CD4 +细胞集落，这些集落被认为是早期祖细胞即树突状/朗格汉斯细胞集落形成单位（CFU - DL）的后代。已使用化学成分明确的无血清系统研究这些细胞的细胞因子调节生长，以培养未分级和高度富集的骨髓祖细胞群体。虽然在含有PHA刺激的白细胞条件培养基（PHA - LCM）的富含血清的培养物中未分级细胞生长最佳，但即使在没有PHA - LCM的情况下，在血清中也观察到CFU - DL的增殖欠佳。当粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）、白细胞介素 - 3（IL - 3）、粒细胞集落刺激因子（G - CSF）和巨噬细胞集落刺激因子（M - CSF）以对粒细胞集落形成单位（CFU - G）和巨噬细胞集落形成单位（CFU - M）生长最佳的水平存在时，在无血清条件下未观察到集落。向这些细胞因子中添加IL - 1α刺激了少量的CFU - DL。然而，在GM - CSF和IL - 3存在的情况下，肿瘤坏死因子 - α（TNF - α）或肿瘤坏死因子 - β（TNF - β，5 U/ml）在促进生长方面都非常有效，可达最佳生长的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天具有活性，更高浓度的TNF - α而非TNF - β对CFU - DL和CFU - G均有抑制作用。富含CD34 +细胞的群体中髓系祖细胞（CFU - G + CFU - M）和CFU - DL也分别富集到36倍和48倍，并且CD34 +细胞的单细胞培养产生了包含CD1a +树突状细胞和CD1a -巨噬细胞的单个集落。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，并且在体外的进一步发育依赖于造血生长因子和TNF。
