title: Induction of T-cell-mediated skin disease specific for antigen transgenically expressed in keratinocytes.
abstract: Transgenic mice were generated to establish an animal model for T-cell-mediated autoimmune skin disease. A membrane-bound form of OVA (mOVA) was specifically expressed under the control of the keratin 5 (K5) promoter in the epidermal and hair follicular keratinocytes of mice. Syngeneic, wild-type mice rejected the skin grafts of K5-mOVA mice with the generation of OVA-specific CTL. To study the CTL response against K5-mOVA skin, we used OT-I transgenic mice, which produce K(b)-restricted, OVA-specific CD8+ T cells. Accelerated rejection of K5-mOVA skin was demonstrated when transplanted onto OT-I mice. Furthermore, OT-I cells, when adoptively transferred into K5-mOVA mice, underwent activation and vigorous proliferation in the skin-draining lymph nodes. A bone-marrow-reconstitution assay demonstrated that K(b) presentation by bone-marrow-derived cells, but not epithelial cells, was required for this response, indicating that cross-priming was the basis for immunity in this model. Finally, transferred OT-I cells, activated by cross-priming, targeted the skin of K5-mOVA mice, resulting in development of skin lesions that were reminiscent of toxic epidermal necrolysis. We conclude that our system provides a useful model for autoimmune skin diseases and will aid understanding of the pathomechanism of drug eruption, viral exanthema, and graft-versus-host disease.
authors.affiliation: Department of Dermatology, Course of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Azukizawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kosaka
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Sano
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Isao
authors.initials: I
authors.lastname: Takahashi
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Gao
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sumikawa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itami
mesh_terms: D000818:Animals; D015603:Keratinocytes / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D012871:Skin Diseases / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D010047:Ovalbumin