A unified theory of central tolerance in the thymus.
Non-deletional tolerance resulting in the generation of regulatory T cells within the thymus is a key mechanism for the establishment of immunological self-tolerance. How the high-affinity self-reactive regulatory T cells escape negative selection and what type of antigen-presenting cells positively select them within the thymus are unsolved questions. Previous studies suggest that thymic epithelial cells are crucial for the positive selection of regulatory T cells in thymus. A recent study from my group shows that a subset of dendritic cells (that have been "educated" by the thymic stromal lymphopoietin molecule produced by a thymic cell type known as Hassall's corpuscles) positively select regulatory T cells within the medulla of human thymus. Here, I discuss the implications and historical context of this new result and suggest that a subset of mature dendritic cells within the thymic medulla protects the medium- to high-affinity self-reactive T cells from negative deletion and induces their differentiation into regulatory T cells in the thymus.
Liu
Yong-Jun
YJ
Department of Immunology, and Center of Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. jyliu@mdanderson.org
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
D051543:Hepatocyte Nuclear Factor 3-gamma