This study investigates the mechanism by which regulatory T (Treg) cells control autoimmune responses in nonobese diabetic (NOD) mice, a model of type 1 diabetes. Using two-photon laser-scanning microscopy (TPLSM), the authors analyzed the interaction between Treg cells and antigen-presenting dendritic cells (DCs) in lymph nodes. They found that Treg cells swarmed and arrested in the presence of autoantigens, inhibiting the activation and proliferation of islet antigen-specific CD4+CD25− T helper cells (TH cells). However, there were no stable associations between Treg and TH cells during active suppression. Instead, Treg cells interacted directly with DCs bearing islet antigens, and these interactions preceded the inhibition of TH cell activation. The study also demonstrated that Treg cells can prevent the priming of autoreactive TH cells in lymph nodes, even when transferred together with pathogenic TH cells. These findings suggest that Treg cells regulate autoimmune responses by altering the function of DCs and preventing the activation of autoreactive TH cells.This study investigates the mechanism by which regulatory T (Treg) cells control autoimmune responses in nonobese diabetic (NOD) mice, a model of type 1 diabetes. Using two-photon laser-scanning microscopy (TPLSM), the authors analyzed the interaction between Treg cells and antigen-presenting dendritic cells (DCs) in lymph nodes. They found that Treg cells swarmed and arrested in the presence of autoantigens, inhibiting the activation and proliferation of islet antigen-specific CD4+CD25− T helper cells (TH cells). However, there were no stable associations between Treg and TH cells during active suppression. Instead, Treg cells interacted directly with DCs bearing islet antigens, and these interactions preceded the inhibition of TH cell activation. The study also demonstrated that Treg cells can prevent the priming of autoreactive TH cells in lymph nodes, even when transferred together with pathogenic TH cells. These findings suggest that Treg cells regulate autoimmune responses by altering the function of DCs and preventing the activation of autoreactive TH cells.