Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice

The in vivo mechanism of regulatory T cell (T-reg cell) function in controlling autoimmunity remains controversial. Here we have used two-photon laser-scanning microscopy to analyze lymph node priming of diabetogenic T cells and to delineate the mechanisms of T-reg cell control of autoimmunity in vivo. Islet antigen-specific CD4(+)CD25(-) T helper cells (T-H cells) and T-reg cells swarmed and arrested in the presence of autoantigens. These T-H cell activities were progressively inhibited in the presence of increasing numbers of T-reg cells. There were no detectable stable associations between T-reg and T-H cells during active suppression. In contrast, T-reg cells directly interacted with dendritic cells bearing islet antigen. Such persistent T-reg cell-dendritic cell contacts preceded the inhibition of T-H cell activation by dendritic cells, supporting the idea that dendritic cells are central to T-reg cell function in vivo.