Spontaneous large-scale lymphoid neogenesis and balanced autoimmunity versus tolerance in the stomach of H+/K+-ATPase-reactive TCR transgenic mouse.
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 alpha 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.
Katakai
Tomoya
T
Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nomura
Takashi
T
Gonda
Hiroyuki
H
Sugai
Manabu
M
Agata
Yasutoshi
Y
Nishio
Akiyoshi
A
Masuda
Tohru
T
Sakaguchi
Shimon
S
Shimizu
Akira
A
D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases; D015551:Autoimmunity; D002828:Choristoma; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology* / Q000473:pathology; D005756:Gastritis / Q000276:immunology; D017506:H(+)-K(+)-Exchanging ATPase / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013272:Stomach Diseases / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D011948:Receptors, Antigen, T-Cell; D017506:H(+)-K(+)-Exchanging ATPase