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

Abstract

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 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.

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.

• Authors: Yi-Ling Chen, Jung-Hua Fang, Ming-Derg Lai, Yan-Shen Shan
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 14 Issue 38 Pg. 5797-809 (Oct 14 2008) ISSN: 1007-9327 [Print] United States
• PMID: 18855977 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Ccr1 protein, mouse
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• RNA, Messenger
• Receptors, CCR1
• Receptors, CCR5
• L-Selectin
• Interleukin-10
• Benzo(a)pyrene

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• Apoptosis
• Benzo(a)pyrene
• Carcinoma (chemically induced, epidemiology, pathology)
• Cell Proliferation
• Female
• Forkhead Transcription Factors (metabolism)
• Injections, Intraperitoneal
• Interleukin-10 (metabolism)
• L-Selectin (metabolism)
• Lymph Nodes (immunology)
• Mice
• Mice, Inbred ICR
• Papilloma (chemically induced, immunology, pathology)
• RNA, Messenger (metabolism)
• Receptors, CCR1 (metabolism)
• Receptors, CCR5 (metabolism)
• Stomach Neoplasms (chemically induced, immunology, pathology)
• T-Lymphocytes, Regulatory (immunology)
• Time Factors