Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In type 1 (insulin-dependent) diabetes mellitus (IDDM) CD8+ T cells represent the majority of lymphocytes which infiltrate the pancreatic islets during beta cell destruction. Soluble CD8 antigen (sCD8) has been shown to correlate with CD8 cell subset activation. In this study we measured by ELISA sCD8 levels in sera from: 33 newly diagnosed IDDM patients; 29 type 1 diabetics with duration of disease more than 1 year; 37 healthy siblings of IDDM patients; 19 healthy controls. Sera from both groups of IDDM patients and from healthy siblings exhibited soluble CD8 mean levels significantly higher than controls (P = 0.0001, P < 0.003, P < 0.03 respectively). Soluble CD8 levels above the normal range (mean +/- 2 s.d. of controls) were found in a percentage of newly diagnosed subjects (54.5%) significantly higher than in subjects with a long-standing duration of disease (6.9%, P < 0.0005) and healthy siblings (16.2%, P < 0.002). Our results suggest that the raised levels of soluble CD8 near to diabetes onset may indicate the activation of CD8+ T cells probably responsible for the autoimmune beta cell destruction.
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PMID:High serum levels of soluble CD8 in insulin-dependent diabetes. 830 3

For unknown reasons, autoimmune diseases such as type 1 diabetes develop after prolonged periods of inflammation of mononuclear cells in target tissues. Here we show that progression of pancreatic islet inflammation to overt diabetes in nonobese diabetic (NOD) mice is driven by the 'avidity maturation' of a prevailing, pancreatic beta-cell-specific T-lymphocyte population carrying the CD8 antigen. This T-lymphocyte population recognizes two related peptides (NRP and NRP-A7) in the context of H-2Kd class I molecules of the major histocompatibility complex (MHC). As pre-diabetic NOD mice age, their islet-associated CD8+ T lymphocytes contain increasing numbers of NRP-A7-reactive cells, and these cells bind NRP-A7/H-2Kd tetramers with increased specificity, increased avidity and longer half-lives. Repeated treatment of pre-diabetic NOD mice with soluble NRP-A7 peptide blunts the avidity maturation of the NRP-A7-reactive CD8+ T-cell population by selectively deleting those clonotypes expressing T-cell receptors with the highest affinity and lowest dissociation rates for peptide-MHC binding. This inhibits the local production of T cells that are cytotoxic to beta cells, and halts the progression from severe insulitis to diabetes. We conclude that avidity maturation of pathogenic T-cell populations may be the key event in the progression of benign inflammation to overt disease in autoimmunity.
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PMID:Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. 1096