Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice.
One of the most intriguing features of gammadelta T cells that reside in murine epithelia is the association of a specific Vgamma/Vdelta usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the "first wave" Vgamma5+ fetal thymocytes and overwhelmingly express the canonical Vgamma5/Vdelta1-TCRs lacking junctional diversity. Targeted disruption of the Vdelta1 gene resulted in a markedly impaired development of Vgamma5+ fetal thymocytes as precursors of DETCs; however, gammadeltaTCR+ DETCs with a typical dendritic morphology were observed in Vdelta1-/- mice and their cell densities in the epidermis were slightly lower than those in Vdelta1+/- epidermis. Moreover, the Vdelta1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes. Vgamma5+ DETCs were predominant in the Vdelta1-/- epidermis, though Vgamma5- gammadeltaTCR+ DETCs were also detected. The Vgamma5+ DETCs showed a typical dendritic shape, gammadeltaTCR(high), and age-associated expansion in epidermis as observed in conventional DETCs of normal mice, whereas the Vgamma5- gammadeltaTCR+ DETCs showed a less dendritic shape, gammadeltaTCR(low), and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular Vgamma/Vdelta-chain usage but requires expression of a limited diversity of gammadeltaTCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.
Hara
H
H
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Kishihara
K
K
Matsuzaki
G
G
Takimoto
H
H
Tsukiyama
T
T
Tigelaar
R E
RE
Nomoto
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000276:immunology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017353:Gene Deletion; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor / Q000276:immunology; D019676:Genes, T-Cell Receptor delta; D005819:Genetic Markers / Q000276:immunology; D006133:Growth Substances / Q000096:biosynthesis; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011487:Protein Conformation; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D013234:Stem Cells; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016207:Cytokines; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D005819:Genetic Markers; D006133:Growth Substances; D016692:Receptors, Antigen, T-Cell, gamma-delta; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors