FOXP3型
医学
免疫系统
调节性T细胞
免疫学
小肠
免疫染色
淋巴结
癌症研究
白细胞介素2受体
T细胞
内科学
免疫组织化学
作者
Fabienne Billiard,Valérie Buard,Marc Benderitter,Christine Linard
标识
DOI:10.1016/j.ijrobp.2010.12.041
摘要
Purpose To assess the frequency and the functional characteristics of one major component of immune tolerance, the CD4+FoxP3+ regulatory T cells (Tregs) in a mouse model of abdominal irradiation. Methods and Materials Mice were exposed to a single abdominal dose of γ-radiation (10 Gy). We evaluated small intestine Treg infiltration by Foxp3 immunostaining and the functional suppressive activity of Tregs isolated from mesenteric lymph nodes. Results Foxp3 immunostaining showed that radiation induced a long-term infiltration of the intestine by Tregs (levels 5.5 times greater than in controls). Co-culture of Tregs from mesenteric lymph nodes with CD4+ effector cells showed that the Tregs had lost their suppressive function. This loss was associated with a significant decrease in the levels of Foxp3, TGF-β, and CTLA-4 mRNA, all required for optimal Treg function. At Day 90 after irradiation, Tregs regained their suppressive activity as forkhead box P3 (Foxp3), transforming growth factor beta (TGF-β), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression returned to normal. Analysis of the secretory function of mesenteric lymph node Tregs, activated in vitro with anti-CD3/anti-CD28 Abs, showed that this dysfunction was independent of a defect in interleukin-10 secretion. Conclusion Radiation caused a long-term accumulation of function-impaired Foxp3+CD4+ Tregs in the intestine. Our study provides new insights into how radiation affects the immune tolerance in peripheral tissues. To assess the frequency and the functional characteristics of one major component of immune tolerance, the CD4+FoxP3+ regulatory T cells (Tregs) in a mouse model of abdominal irradiation. Mice were exposed to a single abdominal dose of γ-radiation (10 Gy). We evaluated small intestine Treg infiltration by Foxp3 immunostaining and the functional suppressive activity of Tregs isolated from mesenteric lymph nodes. Foxp3 immunostaining showed that radiation induced a long-term infiltration of the intestine by Tregs (levels 5.5 times greater than in controls). Co-culture of Tregs from mesenteric lymph nodes with CD4+ effector cells showed that the Tregs had lost their suppressive function. This loss was associated with a significant decrease in the levels of Foxp3, TGF-β, and CTLA-4 mRNA, all required for optimal Treg function. At Day 90 after irradiation, Tregs regained their suppressive activity as forkhead box P3 (Foxp3), transforming growth factor beta (TGF-β), and cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression returned to normal. Analysis of the secretory function of mesenteric lymph node Tregs, activated in vitro with anti-CD3/anti-CD28 Abs, showed that this dysfunction was independent of a defect in interleukin-10 secretion. Radiation caused a long-term accumulation of function-impaired Foxp3+CD4+ Tregs in the intestine. Our study provides new insights into how radiation affects the immune tolerance in peripheral tissues.
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