title: Abdominal γ-radiation induces an accumulation of function-impaired regulatory T cells in the small intestine.
abstract: OBJECTIVE
  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
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire, Direction de la Radioprotection de l'Homme, BP no 17, Fontenay-aux-Roses, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Billiard
authors.forename: Valerie
authors.initials: V
authors.lastname: Buard
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Christine
authors.initials: C
authors.lastname: Linard
mesh_terms: D000005:Abdomen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism*; D005720:Gamma Rays; D007108:Immune Tolerance; D007111:Immunity, Cellular / Q000276:immunology / Q000528:radiation effects; D016753:Interleukin-10 / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D011829:Radiation Dosage; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000528:radiation effects*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10