ABDOMINAL gamma-RADIATION INDUCES AN ACCUMULATION OF FUNCTION-IMPAIRED REGULATORY T CELLS IN THE SMALL INTESTINE

作者：Billiard Fabienne; Buard Valerie; Benderitter Marc; Linard Christine^*

来源：International Journal of Radiation Oncology, Biology, Physics, 2011, 80(3): 869-876.

DOI：10.1016/j.ijrobp.2010.12.041

• Abdominal gamma-irradiation
• Regulatory T cells
• Immune tolerance
• Intestine
• Mesenteric lymph nodes

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 gamma-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-beta, 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-beta), 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.

• 出版日期2011-7-1