Nature Immunology 7, 843 - 850 (2006)
Published online: 9 July 2006; | doi:10.1038/ni1363
Selection of the cutaneous intraepithelial   + T cell repertoire by a thymic stromal determinantJulia M Lewis1, Michael Girardi1, Scott J Roberts1, Susannah D Barbee2, Adrian C Hayday2
& Robert E Tigelaar1, 31
Department of Dermatology and Yale Skin Disease Research Core Center, Yale University School of Medicine, New Haven, Connecticut 06511, USA. 2
Peter Gorer Department of Immunobiology, King's College School of Medicine at Guy's Hospital, London SE1 9RT, UK. 3
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06511, USA.
Correspondence should be addressed to Robert E Tigelaar robert.tigelaar@yale.edu Intraepithelial lymphocytes constitute a group of T cells that express mainly monospecific or oligoclonal T cell receptors (TCRs). Like adaptive TCR  + T cells, intraepithelial lymphocytes, a subset enriched in TCR  + 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 TCR+ 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.
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