CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells.
CD40 cross-linking bypasses the absolute requirement for CD4 T cells during immunization with melanoma antigen gene-modified dendritic cells.
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发表时间：
2001-12
期刊：
影响因子：
11.2
通讯作者：
Antoni Ribas;Lisa H. Butterfield;S. Amarnani;V. Dissette;Donald Kim;Wilson S. Meng;Gustavo A. Miranda;H. Wang;William H. McBride;John A. Glaspy;J. Economou
中科院分区：
文献类型：
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作者：
Antoni Ribas;Lisa H. Butterfield;S. Amarnani;V. Dissette;Donald Kim;Wilson S. Meng;Gustavo A. Miranda;H. Wang;William H. McBride;John A. Glaspy;J. Economou
用树突状细胞（DC）基因免疫小鼠以表达黑色素瘤抗原产生抗原特异性、MHC限制性、CD 4依赖性保护性免疫应答。我们想确定CD 4细胞和MART-1基因修饰的DC的CD 40连接在小鼠黑色素瘤免疫治疗动物模型中的作用。用用MART-1基因（AdVMART 1/DC）腺病毒转导的DC（有或没有CD 40交联）免疫CD 4敲除（CD 4KO）或抗体耗尽的小鼠。在CD 4耗竭的小鼠中不存在肿瘤保护，但是当使用三种不同的构建体接合CD 40受体时，保护被重新建立。用表达Th 1细胞因子白细胞介素（IL）-2，IL-7或IL-12的载体转导DC在该模型中不能再现CD 40介导的成熟信号。用CD 40连接的DC免疫的CD 4KO小鼠中的CD 8 T细胞耗竭消除了保护性应答。对给予野生型C57 BL/6小鼠的AdVMART 1/DC的CD 40交联的合并分析显示抗肿瘤免疫力的总体增强。然而，这种影响在重复研究之间不一致。总之，AdVMART 1转导的DC通过CD 40连接途径的成熟可以促进保护性CD 8 T细胞介导的免疫，这是独立于CD 4 T细胞的帮助。
Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knock-out (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking. Tumor protection was absent in CD4-depleted mice, but protection was reestablished when the CD40 receptor was engaged using three different constructs. Transduction of DCs with vectors expressing the Th1 cytokines interleukin (IL)-2, IL-7, or IL-12 could not reproduce the CD40-mediated maturation signal in this model. CD8 T-cell depletion in CD4KO mice immunized with CD40-ligated DCs abrogated the protective response. Pooled analysis of CD40 cross-linking of AdVMART1/DC administered to wild-type C57BL/6 mice revealed an overall enhancement of antitumor immunity. However, this effect was inconsistent between replicate studies. In conclusion, maturation of AdVMART1-transduced DCs through the CD40 ligation pathway can promote a protective CD8 T-cell-mediated immunity that is independent of CD4 T-cell help.