Compartmentalization of immune regulation by distinct migration behavior of α_E^–CD25⁺ and α_E⁺ Tregs. High expression levels of CD62L enable both α_E^–CD25⁺ Tregs and naive T cells to efficiently enter the antigen-draining lymph node from the bloodstream. Due to preferential recirculation of α_E^–CD25⁺ Tregs through lymph nodes these naive-like Tregs most efficiently inhibit activation and expansion of naive T cells. In contrast, both Th1 effector cells and α_E⁺ Tregs efficiently enter inflamed sites via binding of E/P-selectin ligands (E/P-Lig) to E/P-selectin being up-regulated on inflamed endothelial cells. Due to the preferential accumulation of inflammation-seeking α_E⁺ Tregs the Th1-mediated inflammatory reaction is most efficiently controlled by these effector/memory-like Tregs.