Induction of T-cell-mediated skin disease specific for antigen transgenically expressed in keratinocytes
- Author(s)
- Azukizawa, H; Kosaka, H; Sano, S; Heath, WR; Takahashi, I; Gao, XH; Sumikawa, Y; Okabe, M; Yoshikawa, K; Itami, S;
- Details
- Publication Year 2003-07,Volume 33,Issue #7,Page 1879-1888
- Journal Title
- EUROPEAN JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- 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 keratino-cytes 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-O 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 exan-therna, and graft-versus-host disease.
- Publisher
- WILEY-V C H VERLAG GMBH
- Keywords
- AUTOIMMUNE-DISEASES; ALOPECIA-AREATA; IN-VIVO; LYMPHOCYTES; TOLERANCE; MOUSE; MICE; TRANSPLANTATION; IMMUNITY
- Publisher's Version
- https://doi.org/10.1002/eji.200323630
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2003-07-01 12:00:00