IL-18基因修饰增强肿瘤抗原多肽致敏的树突状细胞体内诱导的抗肿瘤免疫反应

Enhancing effect of IL-18 gene modification on the induction of antitumor immunity by antigen pulsed dendritic cells

目的 :研究肿瘤抗原多肽致敏的白细胞介素 18(IL 18)基因修饰的树突状细胞体内诱导的抗肿瘤免疫反应。方法 :①以Lewis 3LL肺癌细胞特异性抗原肽mut1冲击致敏IL 18基因修饰的骨髓来源的树突状细胞 (DC IL 18 mut1) ,每次用其 1× 10 5 只皮下免疫小鼠 2次 ,然后测定脾细胞的NK活性及CTL杀伤活性 ;②以DC IL 18 mut1每次 2× 10 5 只皮下免疫 1次 ,然后再以 5× 10 53LL细胞攻击 ,在诱导及效应阶段分别以单抗阻断不同免疫成份 ,观察肿瘤的生长。结果 :以DC IL 18 mut1皮下免疫后可诱导出比DC mut1等免疫组更高水平的 3LL肺癌细胞特异性CTL ,并使NK活性明显增加 ;单抗体内阻断实验提示在DC IL 18 mut1免疫诱导阶段 ,CD4 + T细胞和抗原共刺激分子、IFN γ均起到重要作用 ,而效应阶段CD8+ T、IFN γ、NK起作用 ,而CD4 + T则是非必需的。结论 :DC IL 18 mut1皮下免疫后可诱导高水平的抗肿瘤免疫活性 ,其机理与抗原有效提呈、特异性CTL诱导、NK活性增加以及CD4 + 、CD8+ T、NK细胞、IFN γ参与密切相关。

Objective:In order to study the antitumor immune response induced by antigen pulsed,IL 18 gene modified dendritic cells in vivo.Methods:①C57BL/6 mice were immunized twice subcutaneously by tumor antigen peptide pulsed,IL 18 gene modified dendritic cells(DC IL 18/mut1)(1×10 5 cells/mouse),then the NK activity and CTL activity were determined.②In block test,C57BL/6 mice were first immunized once 2×10 5 cells/mouse DC IL 18/mut1 subcutaneously,and then challenged by 5×10 5 3LL Lewis lung cancer cells/mouse with blocking different immune components by monoclonal antibody,the tumor growth were observed.Results:Specific CTL activity and NK activity could be induced most significantly in mice immunized with DC IL 18/mut1.The block test showed that CD4 +T,costimulating pathway,the production of IFN γ involved in the induction phase of immunization with DC IL 18/mut1,and CD8 +T?IFN γ?NK cells involved in the effect phase but CD4 +T cells unnecessary.Conclusion:Immunization with DC msIL 18/mut1 could induce potent antitumor immune activity,whose mechanisms involved effective antigen presentation,increased CTL activity and NK activity,CD4 +?CD8 +T?NK cells incorporation,and the production of IFN γ.