Provision of Continuous Maturation Signaling to Dendritic Cells by RIG-I–Stimulating Cytosolic RNA Synthesis of Sendai Virus
Provision of Continuous Maturation Signaling to Dendritic Cells by RIG-I–Stimulating Cytosolic RNA Synthesis of Sendai Virus
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DOI：
10.4049/jimmunol.0901641
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
S. Okano;Y. Yonemitsu;K. Shirabe;Y. Kakeji;Y. Maehara;M. Harada;Y. Yoshikai;M. Inoue;M. Hasegawa;K. Sueishi
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文献类型：
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作者：
S. Okano;Y. Yonemitsu;K. Shirabe;Y. Kakeji;Y. Maehara;M. Harada;Y. Yoshikai;M. Inoue;M. Hasegawa;K. Sueishi
基于树突状细胞（DC）的免疫疗法具有治疗感染和恶性肿瘤的潜力，但必须详细评估DC的功能能力，特别是成熟和Ag特异性CTL引发。最近的报道表明，DC被提供了连续的成熟信号，在体内转移到患者后，需要引发完整的DC功能。我们在这项研究中证明，rSendai病毒载体（SeV）是一种新的和理想的刺激剂，通过在胞质溶胶中的病毒RNA合成为DC提供连续的成熟信号，导致单核细胞衍生的DC的完全成熟。RIG-I依赖性细胞因子产生和CD 4 T细胞对SeV衍生的辅助Ag的应答对于克服调节性T细胞抑制以在调节性T细胞丰富的环境中引发T细胞-1特异性CTL识别的黑素瘤Ag是必不可少的。通过细胞因子受体或TLR刺激的DC不显示这些功能特征。因此，SeV感染的DC具有DC定向免疫治疗的潜力。
Dendritic cell (DC)-based immunotherapy has potential for treating infections and malignant tumors, but the functional capacity of DC must be assessed in detail, especially maturation and Ag-specific CTL priming. Recent reports suggest that DC that are provided with continuous maturation signals in vivo after transfer into patients are required to elicit the full DC functions. We demonstrate in this study that the rSendai virus vector (SeV) is a novel and ideal stimulant, providing DC with a continuous maturation signal via viral RNA synthesis in the cytosol, resulting in full maturation of monocyte-derived DC(s). Both RIG-I–dependent cytokine production and CD4 T cell responses to SeV-derived helper Ags are indispensable for overcoming regulatory T cell suppression to prime melanoma Ag recognized by T cell-1–specific CTL in the regulatory T cell abundant setting. DC stimulated via cytokine receptors, or TLRs, do not show these functional features. Therefore, SeV-infected DC have the potential for DC-directed immunotherapy.