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Nature Immunology 7, 843–850 (1 August 2006) | doi:10.1038/ni1363

Selection of the cutaneous intraepithelial |[gamma]||[delta]|+ T cell repertoire by a thymic stromal determinant

Julia M Lewis , Michael Girardi , Scott J Roberts , Susannah D Barbee , Adrian C Hayday & Robert E Tigelaar

Intraepithelial lymphocytes constitute a group of T cells that express mainly monospecific or oligoclonal T cell receptors (TCRs). Like adaptive TCRαβ+ T cells, intraepithelial lymphocytes, a subset enriched in TCRγ|[delta]|+ T cells, are proposed to be positively selected by thymically expressed self agonists, yet no direct evidence for this exists at present. Mouse dendritic epidermal T cells are prototypic intraepithelial lymphocytes, displaying an almost monoclonal TCRγ|[delta]|+ repertoire. Here we describe an FVB substrain of mice in which this repertoire was uniquely depleted, resulting in cutaneous pathology. This phenotype was due to failure of dendritic epidermal T cell progenitors to mature because of a heritable defect in a dominant gene used by the thymic stroma to 'educate' the natural, skin-associated intraepithelial lymphocyte repertoire to be of physiological use.