Function of Dendritic cells as Sentinel and Regulator

树突状细胞（DC）根据其表型和发育谱系分为几个亚群，其功能受生理环境的控制。在本研究中，我们通过实验来阐明DC在体内控制免疫应答中的作用，得到了以下结果：1)在Id2^<-/->中观察到向Th2的显著偏差。我们发现CD8α^+ DC亚群的选择性和显著减少，CD8α^-DC亚群比CD8α^-DC亚群产生IL-12的潜力更高。这些结果表明，Id2对于CD8α^+ dc的正常发育是必不可少的，而CD8α^+ dc在Th1/Th2平衡的调节中起着关键作用。2)缺乏IRF-2的小鼠（IRF-2-/-小鼠）在脾脏CD4^+ CD11b^+ DC的发育中表现出明显的选择性缺陷。此外，IRF-2^<-/->小鼠表皮朗格汉斯细胞数量减少。体外逆转录病毒介导的基因转导研究表明，细胞自主需要IRF-2来促进CD4^+ CD11b^+ DC的发展。值得注意的是，在缺乏IRF-2和IFN-α/β受体的小鼠中，DC亚群中的这些异常减少，表明IRF-2通过负的IFN-α/β信号起作用。3) cfse标记的凋亡细胞在体内被dc积极内吞，但仅限于CD8α^+亚群。摄取后，CD8α^+ dc也选择性地向CD4^+和CD8^+ T细胞呈递细胞相关抗原。类似的事件也发生在有文化的人身上。DCs;CD8α+ dc再次选择性地摄取并呈递濒死细胞。相比之下，CD8α^+和CD8α^-DC在培养中都吞噬乳胶颗粒，并且两种DC亚群都存在体内捕获的可溶性卵清蛋白。4) DC原位摄取死细胞后，大量抗原反应性T淋巴细胞被驱动进入细胞周期，但随后T细胞被删除，动物产生耐受性。当死亡细胞随后在感染过程中被处理时，这条通往无反应性的途径应该可以防止或减少自身免疫的发展。5)研究了刺激培养后P-preDC的th极化能力。il -3处理的DC表达OX40L，但几乎不产生IFN-α，导致通过OX40L依赖机制优先启动产生il -4的Th2细胞。相比之下，DC通过病毒感染促进产生IFN-γ的Th1细胞，这取决于它们产生IFN-α的能力，尽管它们同时表达OX40L。然而，在激活过程中，OX40L的表达水平上调，而剩余的IFN-α产生能力下调，因此，长时间SV刺激的DC在一定程度上诱导了Th2反应。少

Dendritic cells (DC) are divided into several subsets by their phenotype and developmental lineage and their functions are controlled under physiological milieu. In this study, we conducted experiments to elucidate role of DC in the control of immune responses in vivo and obtained the following results.1) Significant deviation toward Th2 was observed in Id2^<-/->. We found that a selective and remarkable reduction of the CD8α^+ DC subset, which has higher potential to produce IL-12 than the CD8α^-DC subset. These results demonstrate that Id2 is indispensable for the proper development of CD8α^+ DCs, which play a critical role in the regulation of the Th1/Th2 balance.2) Mice lacking IRF-2 (IRF-2-/-mice) exhibited a marked and selective defect in the development of splenic CD4^+ CD11b^+ DC. Furthermore, the numbers of epidermal Langerhans cells in IRF-2^<-/-> mice were reduced. Studies with in vitro retrovirus-mediated gene transduction showed that IRF-2 was required cell-autonomously fo … More r the development of CD4^+ CD11b^+ DC. Notably, these abnormalities in DC subpopulations diminished in mice lacking both IRF-2 and the IFN-α/β receptor, indicating that IRF-2 acted through negatively IFN-α/β signals.3) The CFSE-labeled apoptotic cells were actively endocytosed by DCs in vivo, but only the CD8α^+ subset. Following uptake, CD8α^+ DCs also selectively present cell-associated antigens to both CD4^+ and CD8^+ T cells. Similar events take place with cultured. DCs ; CD8α+ DCs again selectively take up and present dying cells. In contrast, both CD8α^+ and CD8α^-DCs phagocytose latex particles in culture, and both DC subsets present soluble ovalbumin captured in vivo.4) Following ingestion of the dead cells by DC in situ, large numbers of antigen-reactive T lymphocytes were driven into cell cycle, but then the T cells were deleted and the animals become tolerant. This, pathway to unresponsiveness should prevent or reduce the development of autoimmunity when dying cells are subsequently processed during infection.5) We investigated the Th-polarizing capacity of P-preDC after culture with stimuli. IL-3-treated DC expressed OX40L but produced almost no IFN-α, resulting in the preferential priming of IL-4-producing Th2 cells through OX40L-dependent mechanisms. In contrast, DC by viral infection promoted IFN-γ-producing Th1 cells, depending on their capacity to produce IFN-α, although they simultaneously expressed OX40L. However, the expression level of OX40L was upregulated whereas the, residual IFN-α producing ability was downregulated during activation and, consequently, the DC with prolonged SV stimulation induced Th2 responses to some extent. Less