| First Author | Azukizawa H | Year | 2003 |
| Journal | Eur J Immunol | Volume | 33 |
| Issue | 7 | Pages | 1879-88 |
| PubMed ID | 12811848 | Mgi Jnum | J:131888 |
| Mgi Id | MGI:3774786 | Doi | 10.1002/eji.200323630 |
| Citation | Azukizawa H, et al. (2003) Induction of T-cell-mediated skin disease specific for antigen transgenically expressed in keratinocytes. Eur J Immunol 33(7):1879-88 |
| abstractText | 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. |
