Depletion of CD4+CD25+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma

被引:18
作者
Chen, Yi-Ling [2 ]
Fang, Jung-Hua
Lai, Ming-Derg [3 ]
Shan, Yan-Shen [1 ]
机构
[1] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg,Div Gen Surg, Tainan 70428, Taiwan
[2] Chia Nan Univ Pharm & Sci, Dept Childhood Educ & Nursery, Tainan 70428, Taiwan
[3] Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Coll Med, Tainan 70428, Taiwan
关键词
CD4(+)CD25(+) regulatory T cells; Forestomach tumor; Foxp3;
D O I
10.3748/wjg.14.5797
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: To elucidate the distribution of CD4(+)CD25(+) regulatory T cells (Tregs) in different lymphoid tissues and its local enhancement on tumor growth before and after depletion of CD4(+)CD25(+) Tregs. METHODS: Female ICR mice were gavaged with benzo[a]pyrene (BaP) to induce forestomach carcinoma. CD4(+)CD25(+) Tregs were intra peritoneally depleted with monoclonal antibody PC61. These mice were divided into BaP-only, BaP + IgG, BaP + PC61, and control groups. The forestomach of mice was dissected for histological analysis, and tunnel test was performed for apoptosis of tumor cells. CD4(+)CD25(+) Tregs were sorted from different lymphoid tissues and expression of Foxp3, IL-10, and chemokine receptors was analyzed by flow cytometry semi-quantitative and real-time polymerase chain reaction. RESULTS: The mice gavaged with only BaP showed increased forestomach papilloma and carcinoma at wk 16 and 32. The proportion of CD4(+)CD25(+) Tregs was significantly higher in peri-stomach regional lymph nodes than in other lymphoid tissues. These CD4(+)CD25(+) Tregs in regional lymph nodes expressed higher levels of Foxp3 and IL-10, enriched in the CD62L-subset, and CCR1 and CCR5 chemokine receptors. In mice gavaged with BaP + PC61, the number of tumor nodules and tumor volume decreased significantly with massive infiltrating cells and apoptosis of tumor cells. In the draining regional lymph nodes, the number of CD4(+)CD25(+) Tregs also decreased significantly. CONCLUSION: Inducible and activated CD4(+)CD25(+) Tregs in the draining regional lymph nodes suppress host local immunity during tumor growth. Depletion of CD4(+)CD25(+) Tregs can promote host local immunity to suppress tumor growth. (C) 2008 The WJG Press. All rights reserved.
引用
收藏
页码:5797 / 5809
页数:13
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