title: Does physiological beta cell turnover initiate autoimmune diabetes in the regional lymph nodes?
abstract: The initial immune process that triggers autoimmune beta cell destruction in type 1 diabetes is not fully understood. In early infancy there is an increased beta cell turnover. Recurrent exposure of tissue-specific antigens could lead to primary sensitization of immune cells in the draining lymph nodes of the pancreas. An initial immune injury to the beta cells can be inflicted by several cell types, primarily macrophages and T cells. Subsequently, infiltrating macrophages transfer antigens exposed by apoptotic beta cells to the draining lymph nodes, where antigen presenting cells process and amplify a secondary immune reaction. Antigen presenting cells evolve as dual players in the activation and suppression of the autoimmune reaction in the draining lymph nodes. We propose a scenario where destructive insulitis is caused by recurrent exposure of specific antigens due to the physiological turnover of beta cells. This sensitization initiates the evolution of reactive clones that remain silent in the regional lymph nodes, where they succeed to evade regulatory clonal deletion.
authors.affiliation: Frankel Laboratory, Center for Stem Cell Research, Schneider Children's Medical Center of Israel, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Pearl-Yafe
authors.forename: Svetlana
authors.initials: S
authors.lastname: Iskovich
authors.forename: Ayelet
authors.initials: A
authors.lastname: Kaminitz
authors.forename: Jerry
authors.initials: J
authors.lastname: Stein
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Nadir
authors.initials: N
authors.lastname: Askenasy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology