Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures.
Maturation stages of mouse dendritic cells in growth factor-dependent long-term cultures.
复制标题
小鼠树突状细胞在生长因子依赖性长期培养中的成熟阶段。
DOI：
10.1084/jem.185.2.317
复制
发表时间：
1997-01-20
影响因子：
15.3
通讯作者：
Ricciardi-Castagnoli, P
中科院分区：
文献类型：
--
作者：
Winzler, C;Rovere, P;Rescigno, M;Granucci, F;Penna, G;Adorini, L;Zimmermann, V S;Davoust, J;Ricciardi-Castagnoli, P
在生长因子依赖的未成熟小鼠DC模型系统中，研究了控制树突状细胞（DC）成熟检查点的信号以及表型和功能成熟阶段之间的相关性。定义和表征了DC成熟的三个连续阶段（未成熟、成熟和凋亡）。未成熟的DC（第1阶段）具有低表达的共刺激分子，高度组织化的细胞骨架，粘着斑，和缓慢的运动性，因此，他们是非常有效的抗原摄取和可溶性蛋白的加工。此外，在这个阶段，大多数主要组织相容性复合物II类分子在细胞质隔室内，与不良的同种异体刺激能力一致。细菌或细胞因子在诱导从第1阶段向第2阶段（成熟）进展方面非常有效。共聚焦分析观察到形态学变化，包括F-肌动蛋白解聚和粘着斑蛋白的损失，粘着斑蛋白与获得高运动性相关。天然蛋白抗原的抗原摄取和呈递减少。相反，免疫原性肽和同种异体刺激活性的呈递变得非常有效，并且在抗原呈递后可检测到IL-12 p75的分泌。这种功能性DC成熟以凋亡性细胞死亡结束，并且没有观察到向不成熟表型的逆转。
The signals controlling the checkpoints of dendritic cells (DC) maturation and the correlation between phenotypical and functional maturational stages were investigated in a defined model system of growth factor–dependent immature mouse DC. Three sequential stages of DC maturation (immature, mature, and apoptotic) were defined and characterized. Immature DC (stage 1) had low expression of costimulatory molecules, highly organized cytoskeleton, focal adhesion plaques, and slow motility; accordingly, they were very efficient in antigen uptake and processing of soluble proteins. Further, at this stage most of major histocompatibility complex class II molecules were within cytoplasmic compartments consistent with a poor allostimulatory capacity. Bacteria or cytokines were very efficient in inducing progression from stage 1 towards stage 2 (mature). Morphological changes were observed by confocal analysis including depolymerization of F-actin and loss of vinculin containing adhesive structures which correlates with acquisition of high motility. Antigen uptake and presentation of native protein antigen was reduced. In contrast, presentation of immunogenic peptides and allostimulatory activity became very efficient and secretion of IL-12 p75 was detectable after antigen presentation. This functional DC maturation ended by apoptotic cell death, and no reversion to the immature phenotype was observed.