Tumor immune escape and the role of CD4 regulatory T cells

肿瘤免疫逃逸和CD4调节性T细胞的作用

• 批准号: 13670319
• 负责人: NAKAYAMA Eiichi
• 金额: $ 0.7万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670319/
• 关键词: immune surveillance; regulatory T cells; murine tumors; tumor growth; CTL; methylcholanthrene; p53^<-; ->; CD25

The involvement of two phenotypically different regulatory T cells in tumor growth was investigated. Treatment of BALB/c mice with anti-CD25 mAb (PC61), but not anti-CD4 mAb (GK1.5) before RL male 1 or Meth A inoculation caused the tumor rejection. On the other hand, treatment of BALB/c mice with anti-CD4 mAb (GK1.5) but not anti-CD25 mAb (PC61) on day 6 after inoculation of the same tumors caused rejection. The findings suggested that CD4^+CD25^+ T cells downregulated the rejection response in the early stage of tumor growth. On the other hand, CD4^+CD25^- T cells downregulated the tumor rejection response in the following stage. Both CD4^+CD25^+ and CD4^+CD25^- T cells appeared to inhibit the efficient generation of CTL. Treatment of the mice with anti-CD25 mAb (PC61) before tumor inoculation did not result in continuous tumor growth also suggested that CD4^+CD25^- regulatory T cells did not appear following CD25-depletion. The present study also demonstrated that the treatment of BALB/c mice with anti-CD25 mAb (PC61) at 4 or 6 weeks after 3-methylcholanthrene (3-MC) inoculation retarded tumor occurrence.Furthermore, CD4^+CD25^+ regulatory cells appeared to be involved in tumorgenesis of p53^<-/-> mice. The findings indicated that CD4^+CD^25 regulatory cells are involved in tumorgenesis of established tumor and also tumorgenesis by methylcholanthrene and in p53^<-/-> mice.

研究了两种表型不同的调节性T细胞在肿瘤生长中的参与。在RL雄性1或Meth A接种前，用抗CD 25 mAb（PC 61）而不是抗CD 4 mAb（GK 1.5）处理BALB/c小鼠引起肿瘤排斥。另一方面，在接种相同肿瘤后第6天，用抗CD 4 mAb（GK 1.5）而不是抗CD 25 mAb（PC 61）治疗BALB/c小鼠引起排斥反应。结果表明，CD 4 ^+ CD 25 ^+ T细胞在肿瘤生长早期下调了排斥反应。另一方面，CD 4 ^+ CD 25 ^- T细胞下调了随后阶段的肿瘤排斥反应。CD 4 ^+ CD 25 ^+和CD 4 ^+ CD 25 ^- T细胞似乎都能抑制CTL的有效产生。在肿瘤接种前用抗CD 25单克隆抗体（PC 61）处理小鼠，没有导致肿瘤持续生长，这也表明CD 4 ^+ CD 25 ^-调节性T细胞在CD 25-耗竭后没有出现。本研究还发现，在接种3-甲基胆蒽（3-MC）后4周或6周给予抗CD 25单克隆抗体（PC 61）治疗，可抑制肿瘤的发生，而且CD 4 ^+ CD 25 ^+调节细胞参与了p53^<-/->小鼠的肿瘤发生。研究结果表明，CD 4 ^+CD^25调节细胞参与了已建立肿瘤的肿瘤发生，也参与了甲基胆蒽和p53^<-/->小鼠的肿瘤发生。

项目成果

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Tawara，I.，等人：“在可移植肿瘤生长过程中，两种不同的 CD4+ 调节性 T 细胞相继参与，并通过 CD25 耗竭保护免受 3-甲基胆蒽诱导的肿瘤发生”Jpn。

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