期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：6
页码：3386-3391
DOI：10.1073/pnas.0437899100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The antigen-presenting cells that initiate and maintain MHC class II-associated organ-specific autoimmune diseases are poorly defined. We now describe a new T cell antigen receptor (TCR) transgenic (Tg) model of inflammatory skin disease in which keratinocytes activate and are the primary target of autoreactive CD4+ T cells. We previously generated keratin 14 (K14)-A{beta}b mice expressing MHC class II only on thymic cortical epithelium. CD4+ T cells from K14-A{beta}b mice fail to undergo negative selection and thus have significant autoreactivity. The TCR genes from an autoreactive K14-A{beta}b CD4 hybridoma were cloned to produce a TCR Tg mouse, 2-2-3. 2-2-3 TCR Tg cells are negatively selected in WT C57BL/6 mice but not in 2-2-3/K14-A{beta}b mice. Interestingly, a significant number of mice that express both the K14-A{beta}b transgene and the autoreactive 2-2-3 TCR spontaneously develop inflammatory skin disease with mononuclear infiltrates, induction of MHC class II expression on keratinocytes, and T helper 1 cytokines. Disease can be induced by skin inflammation but not solely by activation of T cells. Thus, cutaneous immunopathology can be directed through antigen presentation by tissue-resident keratinocytes to autoreactive TCR Tg CD4+ cells.
