Where CD4+CD25+ T reg cells impinge on autoimmune diabetes.
J Exp Med
; 202(10): 1387-97, 2005 Nov 21.
Article
em En
| MEDLINE
| ID: mdl-16301745
ABSTRACT
Foxp3 is required for the generation and activity of CD4(+)CD25(+) regulatory T (T reg) cells, which are important controllers of autoimmunity, including type-1 diabetes. To determine where T reg cells affect the diabetogenic cascade, we crossed the Foxp3 scurfy mutation, which eliminates T reg cells, with the BDC2.5 T cell receptor (TCR) transgenic mouse line. In this model, the absence of T reg cells did not augment the initial activation or phenotypic characteristics of effector T cells in the draining lymph nodes, nor accelerate the onset of T cell infiltration of the pancreatic islets. However, this insulitis was immediately destructive, causing a dramatic progression to overt diabetes. Microarray analysis revealed that T reg cells in the insulitic lesion adopted a gene expression program different from that in lymph nodes, whereas T reg cells in draining or irrelevant lymph nodes appeared very similar. Thus, T reg cells primarily impinge on autoimmune diabetes by reining in destructive T cells inside the islets, more than during the initial activation in the draining lymph nodes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Interleucina-2
/
Linfócitos T Reguladores
/
Diabetes Mellitus Tipo 1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article