白介素-18对肝癌裸鼠皮下移植瘤浸润的CD4+T细胞子集的影响

目的探讨白介素-18(IL-18)影响肝癌裸鼠皮下移植瘤浸润的T细胞子集变化的机制。方法以HepG2细胞在裸鼠皮下接种,形成人肝癌皮下移植瘤的同时,以不同剂量IL-18分为4组治疗,4组分别腹腔注射IL-18 0.75,1.00,1.25,0(模型组)μg(0.1 mL)/只,治疗4周,另设正常对照组。观察肿瘤的生长速度和瘤体大小的变化。4周后处死取肿瘤组织和脾组织,免疫磁珠阴选组织中CD4+T细胞,流式细胞术检测各组肿瘤组织及脾组织中IL-17+/IFN-γ-CD4+T(Th17细胞)、IL-17-/IFN-γ+CD4+T(Th1)和IL-17+/IFN-γ+CD4+T细胞的变化。结果 HepG2细胞株建立了裸鼠肝癌皮下移植瘤模型,IL-18抑制人肝癌皮下移植瘤的形成及转移,治疗时间越长剂量越大,抑制效果越明显;与正常对照组比较,肿瘤组织中Th17和IL-17+/IFN-γ+CD4+T细胞浸润数目增加,Th1细胞降低,与脾组织中一致,与正常对照组比较有显著差异(P<0.05)。给IL-18后,随着剂量的增加,Th1细胞增加,IL-17+/IFN-γ+CD4+T细胞和Th17细胞浸润数目降低,给药组与模型组比较有显著差异(P<0.05或0.01)。结论 IL-17+/IFN-γ+CD4+T细胞数目在裸鼠移植瘤及其脾组织中增加,可能是在肿瘤环境中,促进其向Th17细胞分化;IL-18通过诱导IFN-γ的生成促进Th1细胞的生成,呈正反馈效应抑制肿瘤的增殖和转移。

Influence of interleukin-18 on tumor-infiltrating CD4+T cell subset within environment of hepatocellular transplantation tumor model in BALB/c nude mice

Purpose To explore the influence of Interleukin-18(IL-18) on Tumor-infiltrating CD4+T Cell subset within environment of hepatocellular transplantation tumor in BALB/c nude mice.Methods HepG2 cells were inoculated intradermally into the nude mice at concentration of 5×106 to establish tumor model.The model mice were administered ip the different doses of IL-18(0.75,1.00,1.25,0 μg/0.1 mL).After 4 weeks of treatment,the mice were killed and the untouched mouse CD4+T cells were effectively isolated from cells of tumor tissues,tissues intradermally of normal controls and tissues of spleen in which purity was over 90%.Flow cytometry detected the expression of IL-17 +CD4+Tcell(Th17),IFN-γ+CD4+T cell(Th1)and IL-17+IFN-γ+CD4+T cell in CD4+T cells per group.Results IL-18 treatment showed that the longer treatment and the more dosage,the more obvious inhibition effect of tumor.Th17 cell and IL-17+IFN-γ+CD4+T cell infiltrated in tumor were more than those of normal controls with Th1 cell decrease,which was consistent with expression of spleen tissues.There was statistic significance compared with normal controls(P<0.05).As administration of IL-18 dosage increasing,Th1 cell increased,whereas,IL-17+IFN-γ+CD4+T cell and Th17 decreased.There was statistic significance compared with no administrated groups(P<0.05).Conclusion Th17 cell and IL-17+IFN-γ+CD4+T cell infiltrated in tumor and spleen tissues were increased which may be related to Th17 cell differentiation in environment of tumor.IL-18 suppress progression of hepatocellular transplantation tumor by positive feedback effect of IFN-γ production and inducing Th1 cell differentiation.