title: Development of T-cell tolerance utilizes both cell-autonomous and cooperative presentation of self-antigen.
abstract: The development of T-cell self-tolerance in the thymus is important for establishing immune homeostasis and preventing autoimmunity. Here, we review the components of T-cell tolerance, which includes T-cell receptor (TCR) self-reactivity, costimulation, cytokines, and antigen presentation by a variety of antigen-presenting cells (APCs) subsets. We discuss the current evidence on the process of regulatory T (Treg) cell and negative selection and the importance of TCR signaling. We then examine recent evidence showing unique roles for bone marrow (BM)-derived APCs and medullary thymic epithelial cells (mTECs) on the conventional and Treg TCR repertoire, as well as emerging data on the role of B cells in tolerance. Finally, we review the accumulating data that suggest that cooperative antigen presentation is a prominent component of T -ell tolerance. With the development of tools to interrogate the function of individual APC subsets in the medulla, we have gained greater understanding of the complex cellular and molecular events that determine T-cell tolerance.
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Justin S A
authors.initials: JS
authors.lastname: Perry
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Chyi-Song
authors.initials: CS
authors.lastname: Hsieh
mesh_terms: D017951:Antigen Presentation; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000502:physiology*; D060966:Clonal Selection, Antigen-Mediated; D004847:Epithelial Cells / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D017634:Self Tolerance; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell
keywords: T cells; antigen presentation/processing; dendritic cells; medullary thymic epithelial cells; thymus; tolerance/suppression/anergy