title: Regulatory T cells influence blood flow recovery in experimental hindlimb ischaemia in an IL-10-dependent manner.
abstract: OBJECTIVE
  Ischaemic damage is associated with up-regulation of pro-inflammatory cytokines, as well as invasion of leucocytes and lymphocytes to the injured muscle. Regulatory T cells (Tregs) exert suppressive effects on several immune and non-immune cellular elements. We hypothesized that adoptive Treg cell transfer and depletion will influence re-establishment of flow in the hindlimb ischaemia model, and that this effect would be mediated by the cytokine interleukin (IL)-10.
  
  
  RESULTS
  To study the functional role of Tregs in hindlimb ischaemia, we either adoptively transferred Tregs or functionally blocked Tregs by antibodies to CD25. Initially, we showed that the number and function of Tregs is altered after the induction of ischaemia. Treg ablation resulted in reduced blood flow by laser Doppler at Day 7 that became more robust at Day 14. Adoptive Treg transfer led to a significant improvement of flow in the ligated limb. Treg-mediated improvement in flow was abolished by employing blocking anti-IL-10 antibodies.
  
  
  CONCLUSIONS
  These results show that Tregs play an important role in processes that control flow re-establishment after inducible hindlimb ischaemia, and that IL-10 plays a requisite role mediating these effects.
authors: Kaplan Medical Center, Heart Institute, PO Box 1, 76100 Rehovot, Israel affiliated to the Hebrew University, Jerusalem, Israel Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Rinat
authors: R
authors: Sharir
authors: Kaplan Medical Center, Heart Institute, PO Box 1, 76100 Rehovot, Israel affiliated to the Hebrew University, Jerusalem, Israel Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Jonathan
authors: J
authors: Semo
authors: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, Israel.
authors: Aviv
authors: A
authors: Shaish
authors: Neufeld Cardiac Research Institute, Tel Aviv University, Tel-Hashomer, Israel.
authors: Natalie
authors: N
authors: Landa-Rouben
authors: Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Michal
authors: M
authors: Entin-Meer
authors: Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Gad
authors: G
authors: Keren
authors: Kaplan Medical Center, Heart Institute, PO Box 1, 76100 Rehovot, Israel affiliated to the Hebrew University, Jerusalem, Israel jgeorge@bezeqint.net.
authors: Jacob
authors: J
authors: George
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D007511:Ischemia / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: Inflammation; Ischaemia; Lymphocyte; Regulatory T cells