Selection of the cutaneous intraepithelial gammadelta+ T cell repertoire by a thymic stromal determinant.
Intraepithelial lymphocytes constitute a group of T cells that express mainly monospecific or oligoclonal T cell receptors (TCRs). Like adaptive TCR alphabeta+ T cells, intraepithelial lymphocytes, a subset enriched in TCR gammadelta+ 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 gammadelta+ 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.
Lewis
Julia M
JM
Department of Dermatology and Yale Skin Disease Research Core Center, Yale University School of Medicine, New Haven, Connecticut 06511, USA.
Girardi
Michael
M
Roberts
Scott J
SJ
Barbee
Susannah D
SD
Hayday
Adrian C
AC
Tigelaar
Robert E
RE
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D051379:Mice; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D012867:Skin / Q000166:cytology* / Q000276:immunology; D013234:Stem Cells / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D016692:Receptors, Antigen, T-Cell, gamma-delta