Induction of tolerance in type 1 diabetes via both CD4+CD25 + T regulatory cells and T regulatory type 1 cells

Manuela Battaglia, Angela Stabilini, Elena Draghici, Barbara Migliavacca, Silvia Gregori, Ezio Bonifacio, Maria Grazia Roncarolo

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1571-1580
Number of pages10
Issue number6
Publication statusPublished - 2006


  • CFSE, carboxyfluorescein diacetate succinimidyl ester
  • FACS, fluorescence-activated cell sorting
  • ICAM, intracellular adhesion molecule
  • IFN-γ, γ-interferon
  • IL, interleukin
  • mAb, monoclonal antibody
  • TGF, transforming growth factor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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