Regulatory T cells influence blood flow recovery in experimental hindlimb ischaemia in an IL-10-dependent manner

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.