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, 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.

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）