Inhibitory effect of CD4+CD25+CCR6+ regulatory T cells against CD8+T cells in mouse mammary carcinoma model
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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+CCR6regulatory 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.
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Supported by the National High Technology Research and Development Program (973 Program) of China (No. 2007CB512401); the Program for Outstanding Medical Academic Leader of Shanghai (No. LJ06011))