Abstract
Because the development of insulitis and diabetes is predictable in Lyp/Lyp congenic BB rats, we have characterized early islet inflammation in these rats to determine the cell subsets involved in the onset of autoimmune insulitis. Pancreas sections from prediabetic Lyp/Lyp, Lyp/+ and +/+ rats were analyzed by immunohistochemistry. We found W3/25+ cells in the exo- and endocrine tissue from all three genotypes, but intraislet insulitis was never found in Lyp/+ or +/+ rats. The onset of massive, intraislet B- and T-cell infiltration in Lyp/Lyp rats was preceded by Rel B+ cells in and around the islets, followed by ED1+ monocytes/macrophages. Rel B+ cells were more frequent in the parafollicular cortex of pancreatic lymph nodes from Lyp/Lyp than from Lyp/+ and +/+ rats. In the Lyp/Lyp thymus, we found significantly increased expression of IL-12p40 messenger RNA (mRNA; p<0.001), located in the Rel B-protein-rich corticomedullary junction. The NF-KB/Rel B complex specifically transactivates genes involved in antigen presentation in dendritic cells. Rel B+ cells in the islets may therefore mark the onset of autoimmune insulitis and antigen-specific activation of autoreactive T cells in the lymph nodes of diabetes prone Lyp/Lyp BB rats. In the thymus, Rel B+ cells may support the Lyp-dependent development of self-reactive thymocytes by activation of cytokine expression.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Animals
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Animals, Congenic
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Antigen Presentation
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Autoimmune Diseases / genetics*
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Autoimmune Diseases / metabolism
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Autoimmune Diseases / pathology
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Biomarkers
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Diabetes Mellitus, Type 1 / genetics*
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Diabetes Mellitus, Type 1 / metabolism
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Diabetes Mellitus, Type 1 / pathology
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Gene Expression Regulation*
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Genotype
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Image Processing, Computer-Assisted
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In Situ Hybridization
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Interleukin-12 / biosynthesis
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Interleukin-12 / genetics
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Islets of Langerhans / immunology
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Islets of Langerhans / metabolism
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Islets of Langerhans / pathology
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NF-kappa B / metabolism
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Pancreas / immunology
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Pancreas / metabolism
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Pancreas / pathology*
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Pancreatitis / genetics*
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Pancreatitis / immunology
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Pancreatitis / metabolism
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Pancreatitis / pathology
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Prediabetic State / genetics*
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Prediabetic State / immunology
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Prediabetic State / metabolism
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Prediabetic State / pathology
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Proto-Oncogene Proteins / biosynthesis*
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Proto-Oncogene Proteins / genetics
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Rats
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Rats, Inbred BB
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Thymus Gland / metabolism
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Thymus Gland / pathology
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Transcription Factor RelB
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Transcription Factors / biosynthesis*
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Transcription Factors / genetics
Substances
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Biomarkers
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NF-kappa B
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Proto-Oncogene Proteins
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Relb protein, rat
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Transcription Factors
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Transcription Factor RelB
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Interleukin-12