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.
Original language | English |
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Pages (from-to) | 1571-1580 |
Number of pages | 10 |
Journal | Diabetes |
Volume | 55 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2006 |
Keywords
- 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