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


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.


CONCLUSIONS
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.
Department of Surgery, National Cheng Kung University Hospital, Tainan 70428, Taiwan, China.
Yi-Ling
YL
Chen
Jung-Hua
JH
Fang
Ming-Derg
MD
Lai
Yan-Shen
YS
Shan
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D017209:Apoptosis; D001564:Benzo(a)pyrene; D002277:Carcinoma / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D010212:Papilloma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D054389:Receptors, CCR1 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
D000911:Antibodies, Monoclonal; C515301:Ccr1 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D054389:Receptors, CCR1; D019713:Receptors, CCR5; D019041:L-Selectin; D016753:Interleukin-10; D001564:Benzo(a)pyrene