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

Abstract

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. Female ICR mice were gavaged with benzo[a]pyrene (BaP) to induce forestomach carcinoma. CD4(+)CD25(+) Tregs were intraperitoneally 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. 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. 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.