【摘要】 目的:观察CD4+CD25+CCR6+调节性T细胞(简称CCR6+Tregs)体内对CD8+T细胞功能的抑制作用,并探讨其与肿瘤免疫逃逸的关系。方法:建立4T1乳腺癌细胞荷瘤裸鼠模型,FACS分选CCR6+Tregs,检测其Foxp3的表达;FACS分选4T1特异性CD8+T细胞,CFSE标记后分别与CCR6+Tregs或CCR6-Tregs共同过继转输入4T1荷瘤裸鼠体内,观察荷瘤裸鼠肿瘤生长情况和小鼠存活时间;FACS检测肿瘤组织中CD8+T细胞的增殖、细胞因子IFN-γ的产生和颗粒酶B的表达情况。结果:CCR6+Tregs和CCR6-Tregs均高表达Foxp3;CCR6+Tregs和CD8+T细胞共转输组4T1荷瘤裸鼠肿瘤的生长明显快于CCR6-Tregs共转输组和CD8+T细胞单转输组,同时该组荷瘤裸鼠生存时间也明显缩短(P<0.05);CCR6+Tregs和CD8+T细胞共转输组CD8+T细胞的增殖、IFN-γ的产生和颗粒酶B的表达均明显低于CCR6-Tregs共转输组和CD8+T细胞单转输组(P<0.05)。结论:CCR6+Tregs在体内可以有效抑制CD8+T细胞的功能,其在肿瘤免疫逃逸和肿瘤发生、发展中发挥重要作用。更多还原

【Abstract】 Objective:To observe the inhibitory effect of CD4+CD25+CCR6+ regulatory T cells(CCR6+ Tregs) against CD8+T cells in vivo,and to investigate its relationship with tumor immune escape.Methods:Mouse mammary carcinoma models were established by inoculating mammary carcinoma 4T1 cells into nude mice.CCR6+ Tregs were isolated by FACS,and the Foxp3 expression on CCR6+ Tregs was further analyzed by FACS.4T1 specific CD8+T cells were labeled with CFSE after isolation by FACS,and then transferred into 4T1 bearing nude mice combined with or without CCR6+ Tregs or CD4+CD25+CCR6-regulatory T cells(CCR6-Tregs).Tumor growth and survival of 4T1 bearing mice were observed.The proliferation,IFN-γ production,and granzyme B expression of CD8+T cells were examined by FACS.Results:Both CCR6+ Tregs and CCR6-Tregs expressed high levels of Foxp3.The tumors in CCR6+ Tregs and CD8+T cells co-transferred mice grew faster than those in CCR6-Tregs co-transferred and CD8+T cell-transferred groups.The survival period of 4T1 bearing mice was significantly decreased in CCR6+ Tregs co-transferred group(P<0.05).Furthermore,the proliferation,IFN-γ production and granzyme B expression of CD8+ T cells were also dramatically decreased in CCR6+ Tregs co-transferred group compared with those in CCR6-Tregs co-transferred and CD8+ T cell-transferred groups(P<0.05).Conclusion:CCR6+ Tregs can effectively inhibit the function of CD8+ T cells,which might play an important role in tumor immune escape,tumor development and progress.更多还原