Aire regulates the transfer of antigen from mTECs to dendritic cells for induction of thymic tolerance.
Blood
; 118(9): 2462-72, 2011 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-21505196
ABSTRACT
To investigate the role of Aire in thymic selection, we examined the cellular requirements for generation of ovalbumin (OVA)-specific CD4 and CD8 T cells in mice expressing OVA under the control of the rat insulin promoter. Aire deficiency reduced the number of mature single-positive OVA-specific CD4(+) or CD8(+) T cells in the thymus, independent of OVA expression. Importantly, it also contributed in 2 ways to OVA-dependent negative selection depending on the T-cell type. Aire-dependent negative selection of OVA-specific CD8 T cells correlated with Aire-regulated expression of OVA. By contrast, for OVA-specific CD4 T cells, Aire affected tolerance induction by a mechanism that operated independent of the level of OVA expression, controlling access of antigen presenting cells to medullary thymic epithelial cell (mTEC)-expressed OVA. This study supports the view that one mechanism by which Aire controls thymic negative selection is by regulating the indirect presentation of mTEC-derived antigens by thymic dendritic cells. It also indicates that mTECs can mediate tolerance by direct presentation of Aire-regulated antigens to both CD4 and CD8 T cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timo
/
Factores de Transcripción
/
Células Dendríticas
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Supresión Clonal
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Presentación de Antígeno
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Células Epiteliales
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Tolerancia Inmunológica
/
Antígenos
Límite:
Animals
Idioma:
En
Revista:
Blood
Año:
2011
Tipo del documento:
Article
País de afiliación:
Australia