ArticleThe Journal of clinical investigation2001
Constitutive beta cell expression of IL-12 does not perturb self-tolerance but intensifies established autoimmune diabetes.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 29 citations in OpenAlex.
- Autoimmunity in picornavirus infections.Current opinion in virology · 2016Review
- Mechanisms of Beta Cell Dysfunction Associated With Viral Infection.Current diabetes reports · 2015Review
- Interleukin-12 (IL-12)/STAT4 Axis Is an Important Element for β-Cell Dysfunction Induced by Inflammatory Cytokines.PloS one · 2015Article
- Production and function of IL-12 in islets and beta cells.Diabetologia · 2013Article
- Immunology in the clinic review series: focus on type 1 diabetes and viruses: the role of viruses in type 1 diabetes: a difficult dilemma.Clinical and experimental immunology · 2012Review
- Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperation.The Journal of clinical investigation · 2006Article
- T cells infiltrate the brain in murine and human transmissible spongiform encephalopathies.Journal of virology · 2003Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
To analyze the function of the Th1-promoting cytokine IL-12 in vivo, we generated transgenic (tg) mice (RIP-IL12 mice) whose pancreatic beta cells constitutively express bioactive IL-12 or one of its components, p35 or p40. In contrast to non-tg littermates or single-tg RIP-p35 and RIP-p40 mice, RIP-IL12 mice developed a marked pancreatic infiltration of lymphocytes and macrophages, mainly around islets. Expression of bioactive IL-12 primarily upregulated transcript levels of IFN-inducible protein-10 (IP-10), RANTES, IFN-gamma, and TNF-alpha in the pancreas. Despite the substantial recruitment of mononuclear cells, no biochemical or clinical disease was evident in the exocrine or endocrine pancreas. Coexpression of lymphocytic choriomeningitis virus (LCMV) proteins with IL-12 in the beta cells failed to spontaneously activate or expand antigen-specific anti-self/viral T cells in uninfected tg animals. However, when RIP-IL12 x RIP-LCMV tg mice were infected with LCMV, antigen-specific anti-self/viral T cells were induced, which led to an acceleration in the kinetics and severity of insulin-dependent diabetes mellitus (IDDM). Thus, the ectopic expression of IL-12 does not spontaneously break tolerance and activate antigen-specific T cells in the periphery, but it does worsen ongoing autoimmune disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.