Cutting Edge: Tissue Antigen Expression Levels Fine-Tune T Cell Differentiation Decisions In Vivo.
J Immunol
; 205(10): 2577-2582, 2020 11 15.
Article
en En
| MEDLINE
| ID: mdl-33037141
ABSTRACT
Immune homeostasis in peripheral tissues is, to a large degree, maintained by the differentiation and action of regulatory T cells (Treg) specific for tissue Ags. Using a novel mouse model, we have studied the differentiation of naive CD4+ T cells into Foxp3+ Treg in response to a cutaneous Ag (OVA). We found that expression of OVA resulted in fatal autoimmunity and in prevention of peripheral Treg generation. Inhibiting mTOR activity with rapamycin rescued the generation of Foxp3+ T cells. When we varied the level of Ag expression to modulate TCR signaling, we found that low Ag concentrations promoted the generation of Foxp3+ T cells, whereas high levels expanded effector T cells and caused severe autoimmunity. Our findings indicate that the expression level of tissue Ag is a key determinant of the balance between tissue-reactive effector and peripheral Foxp3+ T cells, which determines the choice between tolerance and autoimmunity.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Autoinmunes
/
Activación de Linfocitos
/
Diferenciación Celular
/
Subgrupos de Linfocitos T
/
Linfocitos T Reguladores
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Austria