Thymic stromal cell specialization and the T-cell receptor repertoire.
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.
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D
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Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Reilly
C R
CR
Burkly
L C
LC
DeKoning
J
J
Laufer
T M
TM
Glimcher
L H
LH
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
D011948:Receptors, Antigen, T-Cell