{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:35:04Z","timestamp":1791178504521,"version":"4.1.0"},"reference-count":51,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,11,17]]},"abstract":"<jats:p>It has been established that insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice results from a CD4+ and CD8+ T cell\u2013dependent autoimmune process directed against the pancreatic beta cells. The precise roles that beta cell\u2013reactive CD8+ and CD4+ T cells play in the disease process, however, remain ill defined. Here we have investigated whether naive beta cell\u2013specific CD8+ and CD4+ T cells can spontaneously accumulate in pancreatic islets, differentiate into effector cells, and destroy beta cells in the absence of other T cell specificities. This was done by introducing Kd\u2013 or I-Ag7\u2013restricted beta cell\u2013specific T cell receptor (TCR) transgenes that are highly diabetogenic in NOD mice (8.3- and 4.1-TCR, respectively), into recombination-activating gene (RAG)-2\u2013deficient NOD mice, which cannot rearrange endogenous TCR genes and thus bear monoclonal TCR repertoires. We show that while RAG-2\u2212\/\u2212 4.1-NOD mice, which only bear beta cell\u2013specific CD4+ T cells, develop diabetes as early and as frequently as RAG-2+ 4.1-NOD mice, RAG-2\u2212\/\u2212 8.3-NOD mice, which only bear beta cell\u2013specific CD8+ T cells, develop diabetes less frequently and significantly later than RAG-2+ 8.3-NOD mice. The monoclonal CD8+ T cells of RAG-2\u2212\/\u2212 8.3-NOD mice mature properly, proliferate vigorously in response to antigenic stimulation in vitro, and can differentiate into beta cell\u2013cytotoxic T cells in vivo, but do not efficiently accumulate in islets in the absence of a CD4+ T cell\u2013derived signal, which can be provided by splenic CD4+ T cells from nontransgenic NOD mice. These results demonstrate that naive beta cell\u2013 specific CD8+ and CD4+ T cells can trigger diabetes in the absence of other T or B cell specificities, but suggest that efficient recruitment of naive diabetogenic beta cell\u2013reactive CD8+ T cells to islets requires the assistance of beta cell\u2013reactive CD4+ T cells.<\/jats:p>","DOI":"10.1084\/jem.186.10.1663","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:49:30Z","timestamp":1027702170000},"page":"1663-1676","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":301,"title":["Spontaneous Autoimmune Diabetes in Monoclonal T Cell Nonobese Diabetic Mice"],"prefix":"10.1084","volume":"186","author":[{"given":"Joan","family":"Verdaguer","sequence":"first","affiliation":[{"name":"From the Department of Microbiology and Infectious Diseases, and Julia McFarlane Diabetes Research Centre, The University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Schmidt","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Infectious Diseases, and Julia McFarlane Diabetes Research Centre, The University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelaziz","family":"Amrani","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Infectious Diseases, and Julia McFarlane Diabetes Research Centre, The University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Anderson","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Infectious Diseases, and Julia McFarlane Diabetes Research Centre, The University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuzhat","family":"Averill","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Infectious Diseases, and Julia McFarlane Diabetes Research Centre, The University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pere","family":"Santamaria","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Infectious Diseases, and Julia McFarlane Diabetes Research Centre, The University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[1997,11,17]]},"reference":[{"key":"2023072507195835200_B1","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/0952-7915(94)90011-6","article-title":"Genetic and pathogenic basis of autoimmune diabetes in NOD mice","volume":"6","author":"Serreze","year":"1994","journal-title":"Curr Opin Immunol"},{"key":"2023072507195835200_B2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0092-8674(00)81106-X","article-title":"Insulin-dependent diabetes mellitus","volume":"85","author":"Tisch","year":"1996","journal-title":"Cell"},{"key":"2023072507195835200_B3","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1084\/jem.166.4.823","article-title":"Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. 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