Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that destroys the insulin-secreting β-cells of the pancreas. It is now possible to predict those candidates that will progress to T1D before the full onset of the disease. Prevention of uncontrollable autoimmunity against β-cells in therapies for T1D is mandatory to preserve the β-cell mass. Therefore, immunomodulatory strategies directed to inhibiting the activity of self-reactive T cell clones as well as induction of regulatory T cells would be beneficial for prevention of T1D or recurrence of β-cell autoimmunity against islet cell allografts.