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* Center for Genomic Medicine, Graduate School of Medicine,
Department of Experimental Pathology, Institute for Frontier Medical Sciences,
Horizontal Medical Research Organization, Kyoto University, Kyoto, Japan;
Department of Gastroenterology and Hepatology,
¶ Translational Research Center, Kyoto University Hospital, Kyoto, Japan; and
|| Uji Takeda Hospital, Uji, Japan
Autoimmunity is often accompanied by the development of ectopic lymphoid tissues in the target organ, and these tissues have been believed to have close relevance to the severity of the disease. However, the true relationship between the extent of such lymphoid structures and the intensity or type of immune responses mediated by self-reactive T cells has remained unclear. In the present study, we generated transgenic mice expressing TCR from an autoimmune gastritis (AIG)-inducing Th1 cell clone specific for one of the major stomach self-Ags, H+/K+-ATPase 
subunit. The transgenic mice spontaneously develop massive lymphoid neogenesis with a highly organized tissue structure in the gastric mucosa, demonstrating Ag-specific, T cell-mediated induction of the lymphoid tissues. Nevertheless, the damage of surrounding tissue and autoantibody production were considerably limited compared with those in typical AIG induced by neonatal thymectomy. Such a moderate pathology is likely due to the locally restricted activation and Th2 skewing of self-reactive T cells, as well as the accumulation of naturally occurring regulatory T cells in the target organ. Altogether, the findings suggest that lymphoid neogenesis in chronic autoimmunity does not simply correlate with the destructive response; rather, the overall activation status of the T cell network, i.e., the balance of self-reactivity and tolerance, in the local environment has an impact.
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1 This work was supported by Grants-in-Aid for Science Research on Priority Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
2 Address correspondence and reprint requests to Dr. Akira Shimizu, Translational Research Center, Kyoto University Hospital, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail address: shimizu{at}virus.kyoto-u.ac.jp
3 Abbreviations used in this paper: Treg, regulatory T cell; AIG, autoimmune gastritis; d3-Tx, day 3 thymectomy; GLN, gastric LN; GM, gastric mucosa; HEV, high endothelial venule; H+/K+-ATPase, H+/K+-adenosine triphosphatase; ILF, isolated lymphoid follicle; LN, lymph node; LT, lymphotoxin; MAdCAM-1, mucosal adressin cell adhesion molecule-1; PNAd, peripheral node addressin; SLO, secondary lymphoid organ; TLT, tertiary lymphoid tissue.
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