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。
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, IFNγ 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 cotransferred mice grew faster than those in CCR6 Tregs cotransferred and CD8^＋T celltransferred groups. The survival period of 4T1 bearing mice was significantly decreased in CCR6^＋ Tregs cotransferred group （P〈0.05）. Furthermore, the proliferation, IFNγ production and granzyme B expression of CD8^＋ T cells were also dramatically decreased in CCR6^＋ Tregs cotransferred group compared with those in CCR6 Tregs cotransferred and CD8^＋ T celltransferred 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.
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
北大核心
2009年第5期431-435,共5页
Chinese Journal of Cancer Biotherapy
基金
国家重点基础研究发展计划(973计划)资助项目(No.2007CB512401)
上海市医学领军人才基金资助项目(No.LJ06011)~~
