Dendritic cells require maturation via CD40 to generate protective antitumor immunity.
Dendritic cells require maturation via CD40 to generate protective antitumor immunity.
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DOI：
10.4049/jimmunol.161.5.2094
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发表时间：
1998-09
影响因子：
4.4
通讯作者：
M. Mackey;Jason R. Gunn;C. Maliszewski;Hitoshi Kikutani;R. Noelle;Richard J. Barth
中科院分区：
文献类型：
--
作者：
M. Mackey;Jason R. Gunn;C. Maliszewski;Hitoshi Kikutani;R. Noelle;Richard J. Barth
CD 40/CD 154相互作用在产生保护性细胞介导的肿瘤免疫中的关键作用已在先前得到证实。在此，我们表明，未能产生系统的肿瘤免疫的情况下，CD 40/CD 154相互作用与抑制Th 1型细胞因子的产生肿瘤疫苗接种。此外，保护性抗肿瘤反应可以恢复在CD 40-缺陷的小鼠通过共同管理的CD 40 +/+，而不是CD 40-/-树突状细胞（DC）与肿瘤抗原，表明CD 40是至关重要的成熟和功能的DC在体内。最后，我们证明了IL-12转导的而不是模拟转导的肿瘤疫苗在抗CD 154治疗的和CD 154缺陷的小鼠中诱导全身肿瘤免疫。这些数据表明，在不存在CD 40/CD 154相互作用的情况下，抗肿瘤反应受损是APC功能损伤的结果，即IL-12产生，并且CD 40在体内DC的成熟中起关键作用。
A critical role for CD40/CD154 interactions in the generation of protective cell-mediated tumor immunity has been demonstrated previously. Herein, we show that the failure to generate systemic tumor immunity in the absence of CD40/CD154 interactions correlates with an inhibition of Th1-type cytokine production following tumor vaccination. Furthermore, protective antitumor responses can be restored in CD40-deficient mice by the coadministration of CD40+/+ but not CD40-/- dendritic cells (DCs) with tumor Ag, suggesting that CD40 is critical for the maturation and function of DCs in vivo. Finally, we demonstrate that an IL-12-transduced but not a mock-transduced tumor vaccine induces systemic tumor immunity in anti-CD154-treated and CD154-deficient mice. These data suggest that impaired antitumor responses in the absence of CD40/CD154 interactions are the result of a lesion in APC function, namely IL-12 production, and that CD40 plays a critical role in the maturation of DCs in vivo.