{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T07:33:50Z","timestamp":1779348830786,"version":"3.51.4"},"reference-count":43,"publisher":"American Diabetes Association","issue":"12","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,12,1]]},"abstract":"<jats:p>In comparing the incidence of virally induced type 1 diabetes in F1 crosses of RIP-LCMV mice to three different mouse strains identical at the major histocompatibility complex H-2Db locus, we surprisingly found that disease development was reduced by 80% in F1 crosses to the SV129 genetic background and by 60% after eight backcrosses to the original C57BL\/6 RIP-LCMV mice. In this model, diabetes is strongly dependent on a virally induced H-2Db\u2013restricted cytotoxic T-cell (CTL) response. Importantly, numbers and effector functions of autoaggressive CD4 and CD8 lymphocytes were not decreased in the protected mice, and CTLs were still able to kill syngeneic islet cells in vitro with equal efficacy compared with CTLs from the original RIP-LCMV strain. Furthermore, CTLs were able to extravasate into islets in vivo, and no evidence for induction of regulatory cells was observed. However, regeneration of \u03b2-cells in islets under \u201cattack\u201d occurred only in the protected SV129-crossed animals, whereas it was not evident at any time in any mice that developed diabetes. Thus, genetic factors can \u201coverride\u201d the diabetogenic potential of high numbers of autoaggressive lymphocytes through, for example, increased islet regeneration. This finding has important implications for interpreting numbers and pathogenicity of autoreactive lymphocytes in prediabetic patients of genetically diverse backgrounds.<\/jats:p>","DOI":"10.2337\/diabetes.50.12.2700","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2700-2708","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":13,"title":["Protection From Type 1 Diabetes in the Face of High Levels of Activated Autoaggressive Lymphocytes in a Viral Transgenic Mouse Model Crossed to the SV129 Strain"],"prefix":"10.2337","volume":"50","author":[{"given":"Matthias G.","family":"von Herrath","sequence":"first","affiliation":[{"name":"Immunology and Neuropharmacology, the Scripps Research Institute, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Immunology and Neuropharmacology, the Scripps Research Institute, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ursula","family":"Mo\u0308hrle","sequence":"additional","affiliation":[{"name":"Immunology and Neuropharmacology, the Scripps Research Institute, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan","family":"Coon","sequence":"additional","affiliation":[{"name":"Immunology and Neuropharmacology, the Scripps Research Institute, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Hughes","sequence":"additional","affiliation":[{"name":"Immunology and Neuropharmacology, the Scripps Research Institute, La Jolla, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031207555665600_R1","doi-asserted-by":"crossref","unstructured":"Bach, J.-F: Insulin-dependent diabetes mellitus as an autoimmune disease. 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