Cathepsin L is essential for onset of autoimmune diabetes in NOD mice.
J Clin Invest
; 115(10): 2934-43, 2005 Oct.
Article
em En
| MEDLINE
| ID: mdl-16184198
ABSTRACT
Lysosomal proteases generate peptides presented by class II MHC molecules to CD4+ T cells. To determine whether specific lysosomal proteases might influence the outcome of a CD4+ T cell-dependent autoimmune response, we generated mice that lack cathepsin L (Cat L) on the autoimmune diabetes-prone NOD inbred background. The absence of Cat L affords strong protection from disease at the stage of pancreatic infiltration. The numbers of I-A(g7)-restricted CD4+ T cells are diminished in Cat L-deficient mice, although a potentially diabetogenic T cell repertoire persists. Within the CD4+ T cell compartments of Cat L-deficient mice, there is an increased proportion of regulatory T cells compared with that in Cat L-sufficient littermates. We suggest that it is this displaced balance of regulatory versus aggressive CD4+ T cells that protects Cat L-deficient mice from autoimmune disease. Our results identify Cat L as an enzyme whose activity is essential for the development of type I diabetes in the NOD mouse.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cisteína Endopeptidases
/
Linfócitos T CD4-Positivos
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Antígenos de Histocompatibilidade Classe II
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Catepsinas
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Subpopulações de Linfócitos T
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Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 1
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article