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The Journal of Immunology, 2000, 165: 3695-3705.
Copyright © 2000 by The American Association of Immunologists

Development of Dendritic Epidermal T Cells with a Skewed Diversity of {gamma}{delta}TCRs in V{delta}1-Deficient Mice1

Hiromitsu Hara*, Kenji Kishihara3,*, Goro Matsuzaki*, Hiroaki Takimoto2,*, Tadasuke Tsukiyama{dagger}, Robert E. Tigelaar{ddagger} and Kikuo Nomoto*

Departments of * Immunology and {dagger} Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; and {ddagger} Department of Dermatology, Section of Immunobiology, Yale Skin Diseases Research Core Center, Yale University, New Haven, CT 06520

One of the most intriguing features of {gamma}{delta} T cells that reside in murine epithelia is the association of a specific V{gamma}/V{delta} usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the "first wave" V{gamma}5+ fetal thymocytes and overwhelmingly express the canonical V{gamma}5/V{delta}1-TCRs lacking junctional diversity. Targeted disruption of the V{delta}1 gene resulted in a markedly impaired development of V{gamma}5+ fetal thymocytes as precursors of DETCs; however, {gamma}{delta}TCR+ DETCs with a typical dendritic morphology were observed in V{delta}1-/- mice and their cell densities in the epidermis were slightly lower than those in V{delta}1+/- epidermis. Moreover, the V{delta}1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes. V{gamma}5+ DETCs were predominant in the V{delta}1-/- epidermis, though V{gamma}5- {gamma}{delta}TCR+ DETCs were also detected. The V{gamma}5+ DETCs showed a typical dendritic shape, {gamma}{delta}TCRhigh, and age-associated expansion in epidermis as observed in conventional DETCs of normal mice, whereas the V{gamma}5- {gamma}{delta}TCR+ DETCs showed a less dendritic shape, {gamma}{delta}TCRlow, and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular V{gamma}/V{delta}-chain usage but requires expression of a limited diversity of {gamma}{delta}TCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.




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