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

[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. Overall design: Three conditions: Wild-type, C2TA knockdown, and C2TA knock-out. For each condition three replicates and in total 9 arrays.