Yao Sheng, Wang Shengdian, Zhu Yuwen, Luo Liqun, Zhu Gefeng, Flies Sarah, Xu Haiying, Ruff William, Broadwater Megan, Choi In-Hak, Tamada Koji, Chen Lieping
Department of Oncology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Blood. 2009 Jun 4;113(23):5811-8. doi: 10.1182/blood-2009-02-203141. Epub 2009 Apr 1.
Programmed death one (PD-1) is an inducible molecule belonging to the immunoglobulin superfamily. It is expressed on activated T and B lymphocytes and plays pivotal roles in the negative regulation of adaptive immune responses. We report here an unexpected finding: that PD-1 could also be induced on splenic dendritic cells (DCs) by various inflammatory stimuli. Adoptive transfer of PD-1-deficient DCs demonstrates their superior capacity to wild-type DCs in innate protection of mice against lethal infection by Listeria monocytogenes. Furthermore, PD-1-deficient mice are also more resistant to the infection than wild-type controls, even in the absence of T and B cells, accompanied by elevated production of DC-derived interleukin-12 and tumor necrosis factor-alpha. Our results reveal a novel role of PD-1 in the negative regulation of DC function during innate immune response.
程序性死亡蛋白1（PD-1）是一种属于免疫球蛋白超家族的可诱导分子。它在活化的T淋巴细胞和B淋巴细胞上表达，并在适应性免疫反应的负调节中起关键作用。我们在此报告一项意外发现：各种炎症刺激也可诱导脾脏树突状细胞（DC）表达PD-1。过继转移PD-1缺陷型DC显示，在对小鼠进行抗单核细胞增生李斯特菌致死性感染的天然保护方面，它们比野生型DC具有更强的能力。此外，即使在没有T细胞和B细胞的情况下，PD-1缺陷型小鼠对感染的抵抗力也比野生型对照更强，同时DC衍生的白细胞介素-12和肿瘤坏死因子-α的产生增加。我们的结果揭示了PD-1在天然免疫反应期间对DC功能的负调节中的新作用。
