Institute of Virology, University of Zurich, Zurich, Switzerland.
Eur J Immunol. 2011 Sep;41(9):2544-55. doi: 10.1002/eji.201041374. Epub 2011 Aug 3.
Cross-presentation is an important mechanism to elicit both immune defenses and tolerance. Although only a few DC subsets possess the machinery required for cross-presentation, little is known about differences in cross-presenting capabilities of DCs belonging to the same subpopulation but localized in different lymphoid organs. In this study, we demonstrate that steady-state thymic CD8(+) DCs can efficiently cross-prime naïve CD8(+) T cells in the absence of costimulation. Surprisingly, cross-priming by splenic CD8(+) DCs was dependent on licensing factors such as GM-CSF. In the absence of GM-CSF, antigen-MHC-class-I complexes were detected on thymic but not on splenic CD8(+) DCs, indicating that the cross-presentation capacity of the thymic subpopulation was higher. The observed cross-priming differences between thymic and splenic CD8(+) DCs did not correlate with differential antigen capture or costimulatory molecules found on the surface of DCs. Moreover, we did not detect overall impairment of antigen presentation, as peptide-loaded splenic CD8(+) DCs were able to induce CD8(+) T-cell proliferation. The observation that thymic CD8(+) DCs are more efficient than splenic CD8(+) DCs in T-cell cross-priming in the absence of licensing factors indicates that the requirements for efficient antigen presentation differ between these cells.
交叉呈递是引发免疫防御和耐受的重要机制。尽管只有少数 DC 亚群具有进行交叉呈递所需的机制,但对于属于同一亚群但位于不同淋巴器官的 DC 之间的交叉呈递能力差异知之甚少。在这项研究中,我们证明静息状态下的胸腺 CD8(+) DC 可以在没有共刺激的情况下有效地交叉呈递幼稚 CD8(+) T 细胞。令人惊讶的是,脾 CD8(+) DC 的交叉呈递依赖于 GM-CSF 等许可因子。在缺乏 GM-CSF 的情况下,抗原-MHC 类-I 复合物仅在胸腺 CD8(+) DC 上检测到,而不在脾 CD8(+) DC 上检测到,这表明胸腺亚群的交叉呈递能力更高。观察到的胸腺和脾 CD8(+) DC 之间的交叉呈递差异与 DC 表面的差异抗原捕获或共刺激分子无关。此外,我们没有检测到抗原呈递的整体受损,因为负载肽的脾 CD8(+) DC 能够诱导 CD8(+) T 细胞增殖。观察到在没有许可因子的情况下,胸腺 CD8(+) DC 在 T 细胞交叉呈递中比脾 CD8(+) DC 更有效,这表明这些细胞对有效抗原呈递的要求不同。