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 |
|---|---|
| Pages (from-to) | 1571-1580 |
| Number of pages | 10 |
| Journal | Diabetes |
| Volume | 55 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2006 |
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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
Cite this
Induction of tolerance in type 1 diabetes via both CD4+CD25 + T regulatory cells and T regulatory type 1 cells. / Battaglia, Manuela; Stabilini, Angela; Draghici, Elena; Migliavacca, Barbara; Gregori, Silvia; Bonifacio, Ezio; Roncarolo, Maria Grazia.
In: Diabetes, Vol. 55, No. 6, 2006, p. 1571-1580.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Induction of tolerance in type 1 diabetes via both CD4+CD25 + T regulatory cells and T regulatory type 1 cells
AU - Battaglia, Manuela
AU - Stabilini, Angela
AU - Draghici, Elena
AU - Migliavacca, Barbara
AU - Gregori, Silvia
AU - Bonifacio, Ezio
AU - Roncarolo, Maria Grazia
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
KW - CFSE, carboxyfluorescein diacetate succinimidyl ester
KW - FACS, fluorescence-activated cell sorting
KW - ICAM, intracellular adhesion molecule
KW - IFN-γ, γ-interferon
KW - IL, interleukin
KW - mAb, monoclonal antibody
KW - TGF, transforming growth factor
UR - http://www.scopus.com/inward/record.url?scp=33746368487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746368487&partnerID=8YFLogxK
U2 - 10.2337/db05-1576
DO - 10.2337/db05-1576
M3 - Article
C2 - 16731819
AN - SCOPUS:33746368487
VL - 55
SP - 1571
EP - 1580
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 6
ER -