Increased endogenous antigen presentation in the periphery enhances susceptibility to inflammation-induced gastric autoimmunity in mice.
Eur J Immunol
; 47(1): 155-167, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-27759162
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H+ /K+ ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice. However, increased presentation of endogenously derived HKα epitopes by dendritic cells (DCs) in the gastric lymph node of IE-H+ /K+ ß transgenic mice (IEß) reduces A23 T-cell tolerance to gastric antigens after inflammatory activation, with subsequent development of gastritis. While HKα-specific A23 T cells from immunised wild-type mice were poorly responsive to in vitro antigen specific activation, A23 T cells from immunised IEß transgenic mice were readily re-activated, indicating loss of T-cell anergy. These findings show that DCs of gastric lymph nodes can maintain tolerance of pathogenic T cells following inflammatory stimulation and that the density of endogenous antigen presented to self-reactive T cells is critical in the balance between tolerance and autoimmunity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autoantígenos
/
Autoinmunidad
/
Presentación de Antígeno
/
Susceptibilidad a Enfermedades
/
Gastritis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
Alemania