Winzler C, Rovere P, Rescigno M, Granucci F, Penna G, Adorini L, Zimmermann V S, Davoust J, Ricciardi-Castagnoli P
CNR Centre of Cellular and Molecular Pharmacology, Milan, Italy.
J Exp Med. 1997 Jan 20;185(2):317-28. doi: 10.1084/jem.185.2.317.
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.
在一个依赖生长因子的未成熟小鼠树突状细胞（DC）的特定模型系统中，研究了控制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。定义并描述了DC成熟的三个连续阶段（未成熟、成熟和凋亡）。未成熟DC（阶段1）共刺激分子表达低，细胞骨架高度有序，有粘着斑，运动缓慢；因此，它们在摄取和处理可溶性蛋白抗原方面非常高效。此外，在此阶段，大多数主要组织相容性复合体II类分子位于细胞质区室中，同种异体刺激能力较差。细菌或细胞因子能非常有效地诱导从阶段1向阶段2（成熟）进展。通过共聚焦分析观察到形态学变化，包括F-肌动蛋白解聚和含纽蛋白的粘着结构丧失，这与获得高运动性相关。天然蛋白抗原的摄取和呈递减少。相反，免疫原性肽的呈递和同种异体刺激活性变得非常高效，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，未观察到向未成熟表型的逆转。
