HLA-DR*0401 expression in the NOD mice prevents the development of autoimmune diabetes by multiple alterations in the T-cell compartment.
Cell Immunol
; 298(1-2): 54-65, 2015.
Article
en En
| MEDLINE
| ID: mdl-26363521
ABSTRACT
Several human HLA alleles have been found associated with type 1 diabetes (T1D), but their precise role is not clearly defined. Herein, we report that a human MHC class II (HLA-DR*0401) allele transgene that has been expressed into NOD (H-2(g7)I-E(null)) mice prone to T1D rendered the mice resistant to the disease. T1D resistance occurred in the context of multi-point T-cell alterations such as (i) skewed CD4/CD8 T-cell ratio, (ii) decreased size of CD4(+)CD44(high) T memory pool, (iii) aberrant TCR Vß repertoire, (iv) increased neonatal number of Foxp3(+) and TR-1(+) regulatory cells, and (v) reduced IFN-γ inflammatory response vs. enhanced IL-10 suppressogenic response of T-cells upon polyclonal and antigen-specific stimulation. The T-cells from NOD/DR4 Tg mice were unable to induce or suppress diabetes in NOD/RAG deficient mice. This study describes a multifaceted regulatory function of the HLA-DR*0401 allele strongly associated with the lack of T1D development in NOD mice.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antígenos HLA-DR
/
Receptores de Antígenos de Linfocitos T alfa-beta
/
Linfocitos T Reguladores
/
Diabetes Mellitus Tipo 1
Límite:
Animals
Idioma:
En
Revista:
Cell Immunol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos