Immune Tolerance Induction by Cortical Thymic Epithelial Cells-초청강연

초록

T cell tolerance is established when the T cells develop to avoid harmful reactivity against self antigens expressed in that thymus. In the periphery, organ specific tolerance can be established by various other mechanisms including anergy, ignorance, and regulatory T cells. Furthermore, antigen-presenting cells lacking costimulatory molecules in peripheral tissues initiate abortive immune responses. The thymic microenvironment is organized to achieve efficient self tolerance by providing signals. The negative selection occurs primarily in the thymic medullary compartment. The major player is the dendritic cell and thymic medullary epithelial cells (mTEC). The role of cortical epithelium in tolerance induction has been controversial. Earlier results have given rise to the idea that the thymic microenvironment is compartmentalized, with positive selection taking place in the cortex and negative selection in the medulla. If this is a true dogma, there will be autoimmune responses to the antigens specifically expressed in the cortical epithelial cells. By targeting LacZ protein as a neoantigen within the TSCOT-expressing thymic epithelium, we demonstrate that TSCOT+CDR1+ TEC alone, without any help from the mTEC or DC, is able to establish deletional tolerance in an AIRE-independent manner with a surprisingly high degree of efficiency.