ESTABLISHMENT OF A CELL-LINE WITH FEATURES OF EARLY DENDRITIC CELL PRECURSORS FROM FETAL MOUSE SKIN
ESTABLISHMENT OF A CELL-LINE WITH FEATURES OF EARLY DENDRITIC CELL PRECURSORS FROM FETAL MOUSE SKIN
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DOI：
10.1002/eji.1830250807
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发表时间：
1995-08-01
影响因子：
5.4
通讯作者：
RICCIARDICASTAGNOLI, P
中科院分区：
文献类型：
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作者：
GIROLOMONI, G;LUTZ, MB;RICCIARDICASTAGNOLI, P
在个体发育过程中，皮肤逐渐由主要组织相容性复合体 II 类阴性树突细胞 (DC) 前体填充，然后成熟为有效的抗原呈递细胞 (APC)。为了更好地表征这些 DC 祖细胞，我们通过用携带 env(AKR)-myc(MH2) 融合基因的逆转录病毒载体感染细胞悬液，从胎鼠皮肤中产生了骨髓细胞系。这些细胞以 FSDC 系为代表，表现出树突状形态，它们在无血清培养基中的增殖受到粒细胞/巨噬细胞集落刺激因子 (GM-CSF) 的促进，但巨噬细胞-CSF 则不促进它们的增殖。 FSDC 表达强的表面膜 ATP/ADPase 活性、2A1 抗原的细胞内染色以及与骨髓前体一致的表面表型：H-2(d.b+)、I-A(d,b+)、CD54(+)、CD11b(+)、CD11c(+)、2.4G2(+)、F4/80(+)、CD44(+)、 2F8(+)、ER-MP 12(-)、Sca-1(+)、Sca-2(+)、NLDC-145(-)、B7.2(+)、B7.1(-)、J11d(-)、B220(-)、Thy-1(-) 和 CD3(-)。 FSDC在初级混合白细胞反应中刺激同种异体或同系不良的T细胞，并在用GM-CSF、GM-CSF和白细胞介素(IL)-4或干扰素-γ(IFN-γ)治疗后显着增强这种功能；相反，干细胞因子、IL-1α和肿瘤坏死因子-α则没有作用。需要用 IFN-γ 进行预培养，以将半抗原呈递给体外引发的 T 细胞。然而，在上述两项测定中，即使在细胞因子激活后，FSDC 的 APC 效力也低于成人表皮朗格汉斯细胞。最后，用半抗原衍生并静脉或皮下注射的 FSDC 可以有效诱导首次接触的同系小鼠的接触敏感性反应。结果表明，胎儿小鼠皮肤被具有巨噬细胞/未成熟DC样表面表型和体内启动能力的骨髓前体定植。这些细胞需要进一步分化和激活信号（例如细胞因子）以在体外表达其抗原呈递潜力。
During ontogeny, the skin is progressively populated by major histocompatibility complex class II-negative dendritic cell (DC) precursors that then mature into efficient antigen-presenting cells (APC). To characterize these DC progenitors better, we generated myeloid cell lines from fetal mouse skin by infecting cell suspensions with a retroviral vector carrying an env(AKR)-myc(MH2) fusion gene. These cells, represented by the line FSDC, displayed a dendritic morphology and their proliferation in serum-free medium was promoted by granulocyte/macrophage colony-stimulating factor (GM-CSF), but not macrophage-CSF. FSDC expressed strong surface-membrane ATP/ADPase activity, intracellular staining for 2A1 antigen, and a surface phenotype consistent with a myeloid precursor: H-2(d.b+), I-A(d,b+), CD54(+), CD11b(+), CD11c(+), 2.4G2(+), F4/80(+), CD44(+), 2F8(+), ER-MP 12(-), Sca-1(+), Sca-2(+), NLDC-145(-), B7.2(+), B7.1(-), J11d(-), B220(-), Thy-1(-), and CD3(-). FSDC stimulated poorly allogenic or syngeneic T cells in the primary mixed-leukocyte reaction, and markedly increased this function after treatment with GM-CSF, GM-CSF and interleukin (IL)-4 or interferon-gamma (IFN-gamma); in contrast, stem cell factor, IL-1 alpha and tumor necrosis factor-alpha had no effect. Preculture with IFN-gamma was required for presentation of haptens to primed T cells in vitro. However, FSDC, even after cytokine activation, were less potent APC than adult epidermal Langerhans cells in both of the above assays. Finally, FSDC derivatized with haptens and injected either intravenously or subcutaneous could efficiently induce contact sensitivity responses in naive syngeneic mice. The results indicate that fetal mouse skin is colonized by myeloid precursors possessing a macrophage/immature DC-like surface phenotype and priming capacity in vivo. These cells need further differentiation and activation signals (e.g. cytokines) to express their antigen presenting potential in vitro.