title: Reducing or increasing β-cell apoptosis without inflammation does not affect diabetes initiation in neonatal NOD mice.
abstract: The presentation of islet antigens in the pancreatic LNs (PLNs) of mice is a developmentally regulated process. It has been hypothesized that, during physiological tissue remodeling, a wave of neonatal β-cell apoptosis may initiate diabetes in autoimmune-prone strains of mice. If true, increasing or decreasing physiological β-cell apoptosis in neonatal NOD mice should alter the time-course of antigen presentation in the PLNs. We used transgenic over-expression of either an anti-apoptotic protein (Bcl-2) or a toxic transgene (rat insulin promoter-Kb) in mouse β cells to reduce or increase neonatal β-cell apoptosis, respectively. Neither intervention affected the timing of antigen presentation in the PLNs or the initiation of islet infiltration. This suggests that under physiological conditions and in the absence of inflammation, neonatal β-cell apoptosis in NOD mice is not the trigger for antigen presentation in the draining LNs.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Emma M
authors.initials: EM
authors.lastname: Carrington
authors.forename: Cameron
authors.initials: C
authors.lastname: Kos
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Krishnamurthy
authors.forename: Janette
authors.initials: J
authors.lastname: Allison
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell