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Title: Abdominal {gamma}-Radiation Induces an Accumulation of Function-Impaired Regulatory T Cells in the Small Intestine

Purpose: To assess the frequency and the functional characteristics of one major component of immune tolerance, the CD4{sup +}FoxP3{sup +} 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{sup +} 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{supmore » +}CD4{sup +} Tregs in the intestine. Our study provides new insights into how radiation affects the immune tolerance in peripheral tissues.« less
Authors:
; ;  [1] ;  [1]
  1. Institut de Radioprotection et de Surete Nucleaire, Direction de la Radioprotection de l'Homme, B.P. no. 17, Fontenay-aux-Roses (France)
Publication Date:
OSTI Identifier:
21587575
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 80; Journal Issue: 3; Other Information: DOI: 10.1016/j.ijrobp.2010.12.041; PII: S0360-3016(11)00029-0; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; GAMMA RADIATION; IMMUNITY; IRRADIATION; LYMPH NODES; LYMPHOCYTES; RADIATION DOSES; SMALL INTESTINE ANIMAL CELLS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY; BODY FLUIDS; CONNECTIVE TISSUE CELLS; DIGESTIVE SYSTEM; DOSES; ELECTROMAGNETIC RADIATION; GASTROINTESTINAL TRACT; INTESTINES; IONIZING RADIATIONS; LEUKOCYTES; LYMPHATIC SYSTEM; MATERIALS; ORGANS; RADIATIONS; SOMATIC CELLS