TNF receptor 1 deficiency increases regulatory T cell function in nonobese diabetic mice.
J Immunol
; 187(4): 1702-12, 2011 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-21734073
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 ß cell-specific, highly diabetogenic TCR transgenic I-A(g7)-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 ß 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fator de Necrose Tumoral alfa
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Linfócitos T Reguladores
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Receptores Tipo I de Fatores de Necrose Tumoral
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Diabetes Mellitus Tipo 1
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Células Secretoras de Insulina
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Austrália