title: Neutralization of interleukin-10 or transforming growth factor-β decreases the percentages of CD4+ CD25+ Foxp3+ regulatory T cells in septic mice, thereby leading to an improved survival.
abstract: OBJECTIVE
  To investigate the role of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) in septic conditions, and to examine the potential of targeting them for the treatment of sepsis.
  
  
  BACKGROUND
  Sepsis-induced immunosuppression has long been considered a factor in late mortality of patients with sepsis. Although Tregs are central to the maintenance of immunologic homeostasis and tolerance, little is known about Treg-mediated immunosuppression in the late stages of sepsis.
  
  
  METHODS
  Peripheral blood mononuclear cells (MNCs) in septic patients and liver or spleen MNCs collected after a cecal ligation and puncture (CLP) model in C57BL/6 mice were examined to evaluate the roles of Tregs and the correlation of transforming growth factor (TGF)-β or interleukin (IL)-10 with their activity. We next examined the effects of neutralization of TGF-β or IL-10 on the percentages of Tregs in CD4+ T cells and the survival rates of septic mice.
  
  
  RESULTS
  The percentages of Tregs in peripheral blood lymphocytes were significantly increased in patients with sepsis, and there was a significantly positive correlation between serum IL-10 levels and the percentage of Tregs. CLP injury increases the percentages of Tregs in the CD4+ T cells in the spleen, and there was a significantly positive correlation between the percentages of Tregs and the serum IL-10 or TGF-β levels. The neutralization of TGF-β or IL-10 decreased the percentages of Tregs in CD4+ T cells, restored the percentages of CD4+ T cells in spleen MNCs, and improved survival rates in septic mice.
  
  
  CONCLUSIONS
  We found an increase in the percentages of Tregs in peripheral blood circulating CD4+ T cells from patients with sepsis, and in splenic MNCs from septic mice, and observed that regulation of Tregs by neutralizing IL-10 or TGF-β might represent a novel strategy for treating the immunosuppressive conditions in sepsis.
authors: Department of Surgery, National Defense Medical College, Saitama, Japan.
authors: Shuhichi
authors: S
authors: Hiraki
authors: Satoshi
authors: S
authors: Ono
authors: Hironori
authors: H
authors: Tsujimoto
authors: Manabu
authors: M
authors: Kinoshita
authors: Risa
authors: R
authors: Takahata
authors: Hiromi
authors: H
authors: Miyazaki
authors: Daizoh
authors: D
authors: Saitoh
authors: Kazuo
authors: K
authors: Hase
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D016022:Case-Control Studies; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005770:Gastrointestinal Neoplasms / Q000601:surgery; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000097:blood / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008026:Ligation / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011183:Postoperative Complications; D018805:Sepsis / Q000097:blood / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000097:blood / Q000276:immunology*
chemical_list: D000906:Antibodies; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10