Integrated Department of Immunology, National Jewish Health, University of Colorado Denver, Denver, CO 80206, USA.
J Exp Med. 2011 Aug 29;208(9):1789-97. doi: 10.1084/jem.20110538. Epub 2011 Aug 22.
Cells undergoing programmed cell death (apoptosis) are removed in situ by macrophages and dendritic cells (DCs) through a specialized form of phagocytosis (efferocytosis). In the lung, there are two primary DC subsets with the potential to migrate to the local lymph nodes (LNs) and initiate adaptive immune responses. In this study, we show that only CD103(+) DCs were able to acquire and transport apoptotic cells to the draining LNs and cross present apoptotic cell-associated antigen to CD8 T cells. In contrast, both the CD11b(hi) and the CD103(+) DCs were able to ingest and traffic latex beads or soluble antigen. CD103(+) DCs selectively exhibited high expression of TLR3, and ligation of this receptor led to enhanced in vivo cytotoxic T cell responses to apoptotic cell-associated antigen. The selective role for CD103(+) DCs was confirmed in Batf3(-/-) mice, which lack this DC subtype. Our findings suggest that CD103(+) DCs are the DC subset in the lung that captures and presents apoptotic cell-associated antigen under homeostatic and inflammatory conditions and raise the possibility for more focused immunological targeting to CD8 T cell responses.
细胞程序性死亡（凋亡）的细胞通过巨噬细胞和树突状细胞（DC）通过一种特殊形式的吞噬作用（胞葬作用）原位清除。在肺部，有两种主要的 DC 亚群，具有迁移到局部淋巴结（LN）并启动适应性免疫反应的潜力。在这项研究中，我们表明只有 CD103(+) DC 能够摄取和运输凋亡细胞到引流的 LNs，并将凋亡细胞相关抗原交叉呈递给 CD8 T 细胞。相比之下，CD11b(hi) 和 CD103(+) DC 均能够摄取和运输乳胶珠或可溶性抗原。CD103(+) DC 选择性地高表达 TLR3，该受体的配体可增强对凋亡细胞相关抗原的体内细胞毒性 T 细胞反应。在缺乏这种 DC 亚型的 Batf3(-/-) 小鼠中证实了 CD103(+) DC 的选择性作用。我们的研究结果表明，CD103(+) DC 是肺部在稳态和炎症条件下捕获和呈递凋亡细胞相关抗原的 DC 亚群，并为更有针对性地针对 CD8 T 细胞反应进行免疫靶向提供了可能性。
