Induction of tolerance in type I diabetes via both CD4+CD25+ T regulatory cells and T regulatory type I cells

Success in developing novel therapies to recommence selftolerance
in autoimmunity depends on the induction of T
regulatory (Tr) cells. Here, we report that rapamycin
combined with interleukin (IL)-10 efficiently blocks type 1
diabetes development and induces long-term immunotolerance
in the absence of chronic immunosuppression in
nonobese diabetic (NOD) mice. Rapamycin mediates accumulation
in the pancreas of suppressive CD4CD25
FoxP3 Tr cells, which prevent diabetes. IL-10 induces Tr
type 1 (Tr1) cells, which reside in the spleen and prevent
migration of diabetogenic T-cells to the draining lymph
nodes. These two Tr cell subsets act in concert to control
diabetogenic T-cells that are still present in long-term
tolerant mice. Rapamycin plus IL-10 treatment, promoting
distinct subsets of Tr cells, may constitute a novel and
potent tolerance-inducing protocol for immune-mediated
diseases.