학술논문
The role of islet antigen presenting cells and the presentation of insulin in the initiation of autoimmune diabetes in the NOD mouse.
Document Type
Article
Source
Subject
*ANTIGEN presenting cells
*ISLANDS of Langerhans
*ANIMAL models of diabetes
*AUTOIMMUNITY
*INSULIN genetics
*LABORATORY mice
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Language
ISSN
0105-2896
Abstract
We have been examining antigen presentation and the antigen presenting cells ( APCs) in the islets of Langerhans of the non-obese diabetic ( NOD) mouse. The purpose is to identify the earliest events that initiate autoimmunity in this confined tissue. Islets normally have a population of macrophages that is distinct from those that inhabit the exocrine pancreas. Also found in NOD islets is a minor population of dendritic cells ( DCs) that bear the CD103 integrin. We find close interactions between beta cells and the two APCs that result in the initiation of the autoimmunity. Even under non-inflammatory conditions, beta cells transfer insulin-containing vesicles to the APCs of the islet. This reaction requires live cells and intimate contact. The autoimmune process starts in islets with the entrance of CD4+ T cells and an increase in the CD103+ DCs. Mice deficient in the Batf3 transcription factor never develop diabetes due to the absence of the CD103/ CD8α lineage of DCs. We hypothesize that the 12-20 peptide of the beta chain of insulin is responsible for activation of the initial CD4+ T-cell response during diabetogenesis. [ABSTRACT FROM AUTHOR]