Lou Yanyan, Liu Chengwen, Kim Grace J, Liu Yong-Jun, Hwu Patrick, Wang Gang
Department of Melanoma Medical Oncology, Center for Cancer Immunology Research, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Immunol. 2007 Feb 1;178(3):1534-41. doi: 10.4049/jimmunol.178.3.1534.
Plasmacytoid dendritic cells (pDC) are capable of producing high levels of type I IFNs upon viral stimulation, and play a central role in modulating innate and adaptive immunity against viral infections. Whereas many studies have assessed myeloid dendritic cells (mDC) in the induction of antitumor immune responses, the role of pDC in antitumor immunity has not been addressed. Moreover, the interaction of pDC with other dendritic cell subsets has not been evaluated. In this study, we analyzed the capacity of pDC in stimulating an Ag-specific T cell response. Immunization of mice with Ag-pulsed, activated pDC significantly augmented Ag-specific CD8(+) CTL responses, and protected mice from a subsequent tumor challenge. Immunization with a mixture of activated pDC plus mDC resulted in increased levels of Ag-specific CD8(+) T cells and an enhanced antitumor response compared with immunization with either dendritic cell subset alone. Synergy between pDC and mDC in their ability to activate T cells was dependent on MHC I expression by mDC, but not pDC, suggesting that pDC enhanced the ability of mDC to present Ag to T cells. Our results demonstrate that pDC and mDC can interact synergistically to induce an Ag-specific antitumor immune response in vivo.
浆细胞样树突状细胞（pDC）在病毒刺激下能够产生高水平的I型干扰素，并在调节针对病毒感染的固有免疫和适应性免疫中发挥核心作用。尽管许多研究评估了髓样树突状细胞（mDC）在诱导抗肿瘤免疫反应中的作用，但pDC在抗肿瘤免疫中的作用尚未得到探讨。此外，pDC与其他树突状细胞亚群的相互作用也未得到评估。在本研究中，我们分析了pDC刺激抗原特异性T细胞反应的能力。用抗原脉冲激活的pDC免疫小鼠可显著增强抗原特异性CD8(+) CTL反应，并保护小鼠免受随后的肿瘤攻击。与单独用任一树突状细胞亚群免疫相比，用激活的pDC加mDC的混合物免疫可导致抗原特异性CD8(+) T细胞水平升高和抗肿瘤反应增强。pDC和mDC激活T细胞能力的协同作用取决于mDC而非pDC的MHC I表达，这表明pDC增强了mDC向T细胞呈递抗原的能力。我们的结果表明，pDC和mDC可协同相互作用以在体内诱导抗原特异性抗肿瘤免疫反应。
