Rinat Sharir1, Jonathan Semo1, Aviv Shaish2, Natalie Landa-Rouben3, Michal Entin-Meer4, Gad Keren4, Jacob George5. 1. 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. 2. The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, Israel. 3. Neufeld Cardiac Research Institute, Tel Aviv University, Tel-Hashomer, Israel. 4. Department of Cardiology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 5. Kaplan Medical Center, Heart Institute, PO Box 1, 76100 Rehovot, Israel affiliated to the Hebrew University, Jerusalem, Israel jgeorge@bezeqint.net.
Abstract
AIMS: 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. METHODS AND 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. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: 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. METHODS AND 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. Published on behalf of the European Society of Cardiology. All rights reserved.
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