Diao Jun, Winter Erin, Chen Wenhao, Xu Feng, Cattral Mark S
Toronto General Hospital Research Institute, University Health Network, University of Toronto, Ontario, Canada.
J Immunol. 2007 Sep 1;179(5):2713-21. doi: 10.4049/jimmunol.179.5.2713.
During steady-state conditions, conventional spleen dendritic cells (DC) turn over every 2-3 days. Recent evidence indicates that in situ proliferation of DC arising from immediate conventional DC precursors is an important contributor to their homeostasis. In this study, we report that replication-competent conventional DC precursors and DC can internalize and transfer model particulate and soluble Ags directly to their DC progeny during cell division. Real-time confocal microscopy and flow cytometry indicated that Ag transmission to progeny was symmetrical, and suggested that other mechanisms of inter-DC Ag transfer were not involved. Soluble protein Ags inherited by DC progeny were presented effectively to Ag-specific T lymphocytes. Furthermore, we show that the number of DC, and the proportion that are actively proliferating, expands several-fold during an immune response against a viral infection. Our results point to an unanticipated mechanism in which DC are continuously replaced from Ag-bearing replication-competent precursor cells that pass Ag molecules onto their progeny through successive cell divisions. Our findings help explain how Ag may persist in a population of DC despite the brief lifespan of individual mature DC.
在稳态条件下，传统的脾脏树突状细胞（DC）每2 - 3天更新一次。最近的证据表明，由直接的传统DC前体产生的DC原位增殖是其稳态的重要贡献因素。在本研究中，我们报告具有复制能力的传统DC前体和DC在细胞分裂过程中能够内化并将模型颗粒性和可溶性抗原直接转移给它们的DC子代。实时共聚焦显微镜和流式细胞术表明，抗原向子代的传递是对称的，并且提示不涉及DC间其他抗原转移机制。DC子代继承的可溶性蛋白质抗原能有效地呈递给抗原特异性T淋巴细胞。此外，我们表明在针对病毒感染的免疫反应期间，DC的数量以及活跃增殖的比例会扩大几倍。我们的结果指出了一种意想不到的机制，即DC不断地从携带抗原的具有复制能力的前体细胞中被替代，这些前体细胞通过连续的细胞分裂将抗原分子传递给它们的子代。我们的发现有助于解释尽管单个成熟DC寿命短暂，但抗原如何在DC群体中持续存在。
