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Silencing of C2TA reveals the autonomous role of medullary thymic epithelial cells in central CD4 T cell tolerance

ABSTRACT: [original title] Tissue-specific silencing of C2TA reveals the autonomous role of medullary thymic epithelial cells in central CD4 T cell tolerance. Medullary thymic epithelial cells (mTECs) serve an essential function in central tolerance through expressing peripheral tissue-antigens. Because these antigens may be transferred to and presented by Dendritic Cells, it is unclear whether, besides being an ‘antigen reservoir’, mTECs also fulfill a critical antigen presenting cellfunction. We found that reducing MHC class II-levels on mTECs through transgenic expression of a C2TA-specific ‘designer miRNA’ resulted in an enlarged polyclonal CD4 single-positive compartment. Less CD4+ thymocytes specific for model-antigens expressed in mTECs were deleted, whereas more antigen-specific Foxp3+ regulatory T cells (Treg) emerged. Our data suggest a substantial autonomous contribution of mTECs to both dominant and recessive mechanisms of CD4 T cell tolerance and support an avidity model of Treg development versus deletion.

ORGANISM(S): Mus musculus

PROVIDER: GSE20276 | GEO | 2010/02/11

SECONDARY ACCESSION(S): PRJNA125365

REPOSITORIES: GEO

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