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 journalArticle

126 Citations (Scopus)

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 languageEnglish
Pages (from-to)1571-1580
Number of pages10
JournalDiabetes
Volume55
Issue number6
DOIs
Publication statusPublished - 2006

Fingerprint

Regulatory T-Lymphocytes
Type 1 Diabetes Mellitus
Sirolimus
Interleukin-10
T-Lymphocytes
Self Tolerance
Inbred NOD Mouse
Immune System Diseases
T-Lymphocyte Subsets
Autoimmunity
Immunosuppression
Pancreas
Spleen
Lymph Nodes
Therapeutics

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 journalArticle

Battaglia, M, Stabilini, A, Draghici, E, Migliavacca, B, Gregori, S, Bonifacio, E & Roncarolo, MG 2006, 'Induction of tolerance in type 1 diabetes via both CD4+CD25 + T regulatory cells and T regulatory type 1 cells', Diabetes, vol. 55, no. 6, pp. 1571-1580. https://doi.org/10.2337/db05-1576
Battaglia, Manuela ; Stabilini, Angela ; Draghici, Elena ; Migliavacca, Barbara ; Gregori, Silvia ; Bonifacio, Ezio ; Roncarolo, Maria Grazia. / Induction of tolerance in type 1 diabetes via both CD4+CD25 + T regulatory cells and T regulatory type 1 cells. In: Diabetes. 2006 ; Vol. 55, No. 6. pp. 1571-1580.
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