Induction of Tolerance in Type 1 Diabetes via Both CD4+CD25+ T Regulatory Cells and T Regulatory Type 1 Cells

Author:

Battaglia Manuela1,Stabilini Angela1,Draghici Elena2,Migliavacca Barbara1,Gregori Silvia1,Bonifacio Ezio2,Roncarolo Maria-Grazia13

Affiliation:

1. San Raffaele Scientific Institute, Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy

2. San Raffaele Scientific Institute, Diabetes and Endocrinology Unit, Milan, Italy

3. Università Vita-Salute San Raffaele, Milan, Italy

Abstract

Success in developing novel therapies to recommence self-tolerance 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 CD4+CD25+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.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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