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TNF Receptor 1 Deficiency Increases Regulatory T Cell Function in Nonobese Diabetic Mice
- Source :
- The Journal of Immunology. 187:1702-1712
- Publication Year :
- 2011
- Publisher :
- The American Association of Immunologists, 2011.
-
Abstract
- TNF has been implicated in the pathogenesis of type 1 diabetes. When administered early in life, TNF accelerates and increases diabetes in NOD mice. However, when administered late, TNF decreases diabetes incidence and delays onset. TNFR1-deficient NOD mice were fully protected from diabetes and only showed mild peri-insulitis. To further dissect how TNFR1 deficiency affects type 1 diabetes, these mice were crossed to β cell-specific, highly diabetogenic TCR transgenic I-Ag7–restricted NOD4.1 mice and Kd-restricted NOD8.3 mice. TNFR1-deficient NOD4.1 and NOD8.3 mice were protected from diabetes and had significantly less insulitis compared with wild type NOD4.1 and NOD8.3 controls. Diabetic NOD4.1 mice rejected TNFR1-deficient islet grafts as efficiently as control islets, confirming that TNFR1 signaling is not directly required for β cell destruction. Flow cytometric analysis showed a significant increase in the number of CD4+CD25+Foxp3+ T regulatory cells in TNFR1-deficient mice. TNFR1-deficient T regulatory cells were functionally better at suppressing effector cells than were wild type T regulatory cells both in vitro and in vivo. This study suggests that blocking TNF signaling may be beneficial in increasing the function of T regulatory cells and suppression of type 1 diabetes.
- Subjects :
- Graft Rejection
medicine.medical_specialty
Regulatory T cell
Immunology
Islets of Langerhans Transplantation
Biology
medicine.disease_cause
T-Lymphocytes, Regulatory
Autoimmunity
Mice
Mice, Inbred NOD
Insulin-Secreting Cells
Internal medicine
medicine
Animals
Transplantation, Homologous
Immunology and Allergy
IL-2 receptor
NOD mice
Mice, Knockout
Type 1 diabetes
Tumor Necrosis Factor-alpha
FOXP3
respiratory system
medicine.disease
Diabetes Mellitus, Type 1
medicine.anatomical_structure
Endocrinology
Receptors, Tumor Necrosis Factor, Type I
Tumor necrosis factor alpha
Insulitis
Signal Transduction
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 187
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....f66a0c1d58c73b823119dde8722beaa0