Background. Recently, it was demonstrated that arteriogenesis is enhanced in mice deficient for regulatory T cells (CD4(+) CD25(+) FoxP3(+) T cell), which can suppress effector T cell responses.... Show moreBackground. Recently, it was demonstrated that arteriogenesis is enhanced in mice deficient for regulatory T cells (CD4(+) CD25(+) FoxP3(+) T cell), which can suppress effector T cell responses. The present study investigates the effects of these regulatory T cells on arteriogenesis in more detail by either specific expanding or depleting regulatory T cells. Methods and materials. Hind limb ischemia was induced by electro-coagulation of the femoral artery in mice. Regulatory T cells were either expanded by injecting mice with a complex of interleukin (IL)-2 with the IL-2 monoclonal antibody JES6-1, or depleted by anti-CD25 antibody or diphtheria toxin (DT)-injections in DEREG mice (DEpletion of REGulatory T cells). Blood flow restoration was monitored using Laser Doppler Perfusion Imaging. Collateral arteries were visualised by immuno-histochemistry. Results. Regulatory T cell expansion led to a moderate though significant suppression of blood flow restoration after ischemia induction. Surprisingly, depletion of regulatory T cells resulted in minor increase on blood flow recovery. However, collateral and capillary densities in the post-ischemic skeletal muscle were significantly increased in DEREG mice depleted for regulatory T cells. The presence of regulatory T cells after ischemia induction when analysed in non-depleted DEREG mice could be demonstrated by GFP staining only in lymph nodes in the ischemic area, and not in the ischemic muscle tissue. Conclusion. The current study demonstrates that, even under conditions of major changes in regulatory T cell content, the contribution of regulatory T cells to the regulation of the arteriogenic response is only moderate. Show less
