title: Thymic stromal cell specialization and the T-cell receptor repertoire.
abstract: Ten years ago, we proposed a model for thymus function in which thymic epithelial cells are primarily responsible for imprinting major histocompatibility complex (MHC)-restricted specificity, and bone marrow-derived macrophages or dendritic cells are responsible for the induction of self-tolerance. Since then, transgenic and knockout models have allowed for a dissection of thymic stromal components in vivo, leading to a new understanding of their specialized functions. We have determined that with regard to class II-restricted CD4 T-cell development, two distinct subsets of thymic epithelium help shape the repertoire: Cortical epithelium appears solely responsible for positive selection, whereas a fucose-bearing subset of medullary epithelium is specialized for negative selection. This absolute separation of positive and negative selection into two distinct spatial and temporal compartments leads to a much simpler view of the process of repertoire selection. Finally, a novel view of the function of the thymic medulla is discussed.
authors.affiliation: Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lo
authors.forename: C R
authors.initials: CR
authors.lastname: Reilly
authors.forename: L C
authors.initials: LC
authors.lastname: Burkly
authors.forename: J
authors.initials: J
authors.lastname: DeKoning
authors.forename: T M
authors.initials: TM
authors.lastname: Laufer
authors.forename: L H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000818:Animals; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000502:physiology
chemical_list: D011948:Receptors, Antigen, T-Cell