The delivery of an antigen from the endocytic compartment into the cytosol for cross-presentation is restricted to early immature dendritic cells
The delivery of an antigen from the endocytic compartment into the cytosol for cross-presentation is restricted to early immature dendritic cells
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DOI：
10.1111/j.1365-2567.2005.02270.x
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发表时间：
2006-01-01
期刊：
影响因子：
6.4
通讯作者：
Minami, M
中科院分区：
文献类型：
--
作者：
Hotta, C;Fujimaki, H;Minami, M
树突状细胞是唯一具有交叉呈递能力的抗原呈递细胞群。然而，对于交叉呈递，细胞内抗原加工途径及其调控机制尚未明确。本研究报告了小鼠骨髓来源的未成熟DC、早期未成熟DC、晚期未成熟DC和完全成熟的d10 +脂多糖DC之间交叉呈递能力的差异。day8 - dc和day10- dc表现出不成熟的表型特征，但在形态上有所不同。day8 - dc可以内化大量外源性可溶性卵清蛋白（OVA），并导致交叉呈现。相比之下，day10- dc不能交叉呈现，尽管它们保持有效的巨噬细胞吞噬。外源性内化的OVA抗原储存在内吞室中。在第8天，内吞室暂时维持在轻度酸性的pH值，在第10天，在摄取抗原后迅速酸化。我们发现，在第8天的dc内，积累在胞吞室中的OVA抗原进入细胞质，但在第10天的dc内却没有。nh4cl处理可以中和酸性内吞腔室和/或延迟内体成熟，恢复day10- dc将储存的OVA抗原从内吞腔室转运到细胞质中。氯化二苯肼处理，使内吞室酸化，减少了在第8天dc内转运的OVA抗原进入细胞质的量。这些数据表明，即使在摄取外源抗原后，只有早期未成熟的DC会干扰内体成熟，然后将抗原转运到细胞质中。
Dendritic cells (DCs) are the only antigen-presenting cell population having a cross-presentation capacity. For cross-presentation, however, the intracellular antigen-processing pathway and its regulatory mechanism have not been defined. Here we report the differences in cross-presentation ability among murine bone marrow-derived immature DC, early immature day8-DC and late immature day10-DC, and fully mature day10 + lipopolysaccharide DC. Day8-DCs and day10-DCs show an immature phenotypic profile but are different in morphology. Day8-DCs can internalize an abundant volume of exogenous soluble ovalbumin (OVA) and result in cross-presentation. In contrast, day10-DCs are not able to cross-present, although they maintain efficient macropinocytosis. Exogenously internalized OVA antigens are stored in the endocytic compartments. The endocytic compartments are temporarily maintained at mildly acidic pH in day8-DCs and are rapidly acidified in day10-DCs after uptake of antigens. We show that OVA antigens accumulated in the endocytic compartments move into the cytosol in day8-DCs but do not in day10-DCs. NH4Cl-treatment, which neutralizes the acidic endocytic compartments and/or delays endosomal maturation, restores day10-DCs for transport the stored OVA antigens from the endocytic compartments into the cytosol. Diphenyleneiodonium chloride-treatment, which acidifies the endocytic compartments, decreases an amount of transported OVA antigen into the cytosol in day8-DCs. These data indicate that only the early immature stage of DC interferes with endosomal maturation, even after uptake of exogenous antigens, and then transports the antigens into the cytosol.