title: Islet inflammation in human type 1 diabetes mellitus.
abstract: Type 1 diabetes mellitus (T1DM) is caused by the selective deletion of pancreatic β-cells in response to an assault mounted within the pancreas by infiltrating immune cells. However, this apparently clear and focussed annunciation conceals a stark reality in which the cellular and molecular events leading to β-cell loss remain poorly understood in humans. This reflects the difficulty of studying these processes in living individuals and the fact that, using pathological specimens, islet inflammation has been analysed in fewer than 200 recent-onset cases of T1DM worldwide, over the past century. Nevertheless, insights have been gained and the composition of the islet infiltrate is being disclosed. This is shown to be primarily lymphocytic in nature, with populations of both CD8+ and CD4+ T cells displaying an autoreactivity against specific islet antigenic peptides. The T cells are often accompanied by influent CD20+ B cells, although new data imply that the proportions of these individual cell types vary and that patients fall into at least two distinct categories having either a hyper-immune (CD20Hi) or a pauci-immune (CD20Lo) phenotype. The overall rate of β-cell decline appears to correlate with these two phenotypes such that hyper-immune patients lose β-cells more quickly and tend to develop disease at an earlier age than those with the pauci-immune profile. In this article, we review the evidence which underpins our current understanding of the aetiology of T1DM and highlight both the established features as well as areas of on-going ambiguity and debate.
authors.affiliation: Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK.
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
authors.forename: Pia
authors.initials: P
authors.lastname: Leete
authors.forename: Alan K
authors.initials: AK
authors.lastname: Foulis
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Richardson
mesh_terms: D018951:Antigens, CD20 / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D050417:Insulin-Secreting Cells / Q000473:pathology*; D007515:Islets of Langerhans / Q000276:immunology / Q000503:physiopathology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D018951:Antigens, CD20
keywords: Insulin; Insulitis; cell death; islets of Langerhans; pancreatic islet cells; β-cell