title: Mechanisms of thymus medulla development and function.
abstract: The development of CD4(+) helper and CD8(+) cytotoxic T-cells expressing the αβ form of the T-cell receptor (αβTCR) takes place in the thymus, a primary lymphoid organ containing distinct cortical and medullary microenvironments. While the cortex represents a site of early T-cell precursor development, and the positive selection of CD4(+)8(+) thymocytes, the thymic medulla plays a key role in tolerance induction, ensuring that thymic emigrants are purged of autoreactive αβTCR specificities. In recent years, advances have been made in understanding the development and function of thymic medullary epithelial cells, most notably the subset defined by expression of the Autoimmune Regulator (Aire) gene. Here, we summarize current knowledge of the developmental mechanisms regulating thymus medulla development, and examine the role of the thymus medulla in recessive (negative selection) and dominant (T-regulatory cell) tolerance.
authors.affiliation: MRC Centre for Immune Regulation, Institute for Biomedical Research, Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK, g.anderson@bham.ac.uk.
authors.forename: Graham
authors.initials: G
authors.lastname: Anderson
authors.forename: Song
authors.initials: S
authors.lastname: Baik
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cowan
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Holland
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: McCarthy
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Parnell
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: White
authors.forename: Peter J L
authors.initials: PJ
authors.lastname: Lane
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jenkinson
authors.forename: William E
authors.initials: WE
authors.lastname: Jenkinson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004847:Epithelial Cells / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D007108:Immune Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*