Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation

• Published in: Nature reviews. Immunology Vol. 19; no. 1; pp. 7 - 18
• Main Authors: Klein, Ludger, Robey, Ellen A., Hsieh, Chyi-Song
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2019; Nature Publishing Group
• Subjects: 631/250/1619/554/1898/1271; 631/250/1620/1840; 631/250/2152/1566/2493; 631/250/38; Animals; Antigens; Autoantigens; Biomedical and Life Sciences; Biomedicine; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell differentiation; Cell Differentiation - immunology; Cell lineage; Clonal deletion; Humans; Immune Tolerance - immunology; Immunological tolerance; Immunology; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Review Article; T cell receptors; T-Lymphocytes, Regulatory - immunology; Thymocytes; Thymocytes - immunology; Thymus
• ISSN: 1474-1733; 1474-1741; 1474-1741
• DOI: 10.1038/s41577-018-0083-6

The diversion of MHC class II-restricted thymocytes into the regulatory T (T reg ) cell lineage is driven by intrathymic encounter of agonist self-antigens in a similar manner to the clonal deletion of thymocytes. Somewhat paradoxically, it thus seems that the expression of an autoreactive T cell receptor is a shared characteristic of T cells that are subject to clonal deletion and T cells that are diverted into the T reg cell lineage. Here, we discuss how thymocyte-intrinsic and thymocyte-extrinsic determinants may specify the choice between these two fundamentally different T cell fates. Self-antigen recognition in the thymus can result in both clonal deletion of developing thymocytes and their diversion into the regulatory T cell lineage. How do thymocyte-intrinsic and thymocyte-extrinsic determinants influence this cell fate choice?