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The role of islet antigen presenting cells and the presentation of insulin in the initiation of autoimmune diabetes in the NOD mouse
Author(s) -
Unanue Emil R.,
Ferris Stephen T.,
Carrero Javier A.
Publication year - 2016
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12430
Subject(s) - nod mice , nod , autoimmunity , islet , biology , antigen presentation , population , insulitis , immunology , antigen , antigen presenting cell , pancreas , beta cell , endocrinology , medicine , diabetes mellitus , t cell , immune system , environmental health
Summary We have been examining antigen presentation and the antigen presenting cells ( APC s) 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 ( DC s) that bear the CD 103 integrin. We find close interactions between beta cells and the two APC s that result in the initiation of the autoimmunity. Even under non‐inflammatory conditions, beta cells transfer insulin‐containing vesicles to the APC s of the islet. This reaction requires live cells and intimate contact. The autoimmune process starts in islets with the entrance of CD 4 + T cells and an increase in the CD 103 + DC s. Mice deficient in the Batf3 transcription factor never develop diabetes due to the absence of the CD 103/ CD 8α lineage of DC s. We hypothesize that the 12–20 peptide of the beta chain of insulin is responsible for activation of the initial CD 4 + T‐cell response during diabetogenesis.