Abdominal γ-radiation induces an accumulation of function-impaired regulatory t cells in the small intestine
Résumé
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. © 2011 Elsevier Inc.
Mots clés
Abdominal irradiation
Coculture
Cytotoxic
Effector cells
Functional characteristics
Immune tolerance
Immune tolerances
Immunostaining
In-control
In-vitro
Interleukin-10
Intestine
Lymph node
Mouse models
Peripheral tissue
Radiation-induced
Small intestine
T cells
Transforming growth factor beta
Body fluids
Cell culture
Irradiation
Seepage
Soil mechanics
Tissue
Radiation
CD3 antibody
cytotoxic T lymphocyte antigen 4
interleukin 10
messenger RNA
monoclonal antibody CD28
transcription factor FOXP3
transforming growth factor beta
article
cell infiltration
gamma radiation
immunohistochemistry
in vitro study
mesentery lymph node
mouse
nonhuman
priority journal
protein expression
regulatory T lymphocyte
small intestine
Abdomen
Animals
Antigens
CD
Forkhead Transcription Factors
Gamma Rays
Immune Tolerance
Immunity
Cellular
Small
Lymph Nodes
Mesentery
Mice
Inbred C57BL
Radiation Dosage
RNA
Messenger
T-Lymphocytes
Regulatory
Transforming Growth Factor beta