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

Journal Article · Fri Jul 01 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.12.041· OSTI ID:21587575

Billiard, Fabienne; Buard, Valerie; Benderitter, Marc ^[1]; Linard, Christine ^[1]

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1. Institut de Radioprotection et de Surete Nucleaire, Direction de la Radioprotection de l'Homme, B.P. no. 17, Fontenay-aux-Roses (France)

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{sup +}CD4{sup +} Tregs in the intestine. Our study provides new insights into how radiation affects the immune tolerance in peripheral tissues.

• OSTI ID: 21587575
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 80, 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); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

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