title: The vicious cycle of apoptotic beta-cell death in type 1 diabetes.
abstract: Autoimmune insulitis, the cause of type 1 diabetes, evolves through several discrete stages that culminate in beta-cell death. In the first stage, antigenic epitopes of B-cell-specific peptides are processed by antigen presenting cells in local lymph nodes, and auto-reactive lymphocyte clones are propagated. Subsequently, cell-mediated and direct cytokine-mediated reactions are generated against the beta-cells, and the beta-cells are sensitized to apoptosis. Ironically, the beta-cells themselves contribute some of the cytokines and chemokines that provoke the immune reaction within the islets. Once this vicious cycle of autoimmunity is fully developed, the fate of the beta-cells in the islets is sealed, and clinical diabetes inevitably ensues. Differences in various aspects of these concurrent events appear to underlie the significant discrepancies in experimental data observed in experimental models that simulate autoimmune insulitis.
authors.affiliation: Frankel Laboratory, Center for Stem Cell Research, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
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; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*
chemical_list: D016207:Cytokines