期刊
BLOOD
卷 118, 期 9, 页码 2462-2472出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-06-286393
关键词
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类别
资金
- NHMRC [171601, 461202, 461204, 257501, 264573, 406700, 454465]
- La Fondation pour la Recherche Medicale (FRM)
- EU [040998]
- Australian Postgraduate Awards
- Eurothymaide and EURAPS
- WEHI
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
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