Background: Ischemic damage is associated with upregulation of pro-inflammatory cytokines, as well as invasion of leukocytes and lymphocytes
into 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 reestablishment of flow in the hindlimb ischemia model and that this effect would be mediated by the cytokine IL-10.
Methods and Results: To study the functional role of Tregs in hindlimb ischemia 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 ischemia. Treg ablation resulted in reduction of 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 completely abolished employing blocking anti-10 antibodies.
Conclusions: These results show that Tregs play an important role in the processes that control flow reestablishment after inducible hindlimb ischemia and that IL-10 plays a requisite role mediating these effects.
