Tolerance Induction and Antigen Presenting Function of TSCOT Specific Thymic Epithelial Cells

초록

Thymic Stromal Co-Transporter (TSCOT) is originally found to be expressed specifically in the thymic epithelial cells (TEC). Its expression in the thymic microenvironment was localized mainly into cortex by RNA and protein expression. By single cell analysis using flow cytometry, TSCOT+ cells are also MHCII+, CDR1/6C3+, CD40+ and CD54+. Surprisingly, a fraction of TSCOT+ cells express high levels of CD80. Expression of costimulatory molecules can explain TSCOT+ cell mediated complete tolerance of self antigens expressed, as tested in the mouse models that LacZ gene was knock into the TSCOT locus (TDLacZ). The highly sensitive tolerance was observed in the presence of broad spectrum of T cell repertoire as well as in the monospecific anti-LacZ specific TCR transgenic mouse. The thymus of TDLacZ mouse contains about 4,300 TSCOT+ cells, each expressing several thousand molecules of the LacZ antigen. Overall, we show that the introduction of a neoantigen into TSCOT-expressing cells is partially independent of Autoimmune Regulatory Element (AIRE) gene expression and suggest a possible application for the deletion of antigen-specific T cells by antigen introduction into TSCOT+ cells.