title: Narrowing in on the anti-β cell-specific T cells: looking 'where the action is'.
abstract: OBJECTIVE
  By necessity, the vast majority of information we have on autoreactive T cells in human type 1 diabetes (T1D) has come from the study of peripheral blood of donors with T1D. It is not clear how representative the peripheral autoreactive T-cell repertoire is of the autoreactive T cells infiltrating the islets in T1D. We will summarize and discuss what is known of the immunohistopathology of insulitis, the T-cell receptor repertoire expressed by islet-infiltrating T cells, and the autoreactivity and function of islet-infiltrating T cells in T1D.
  
  
  RESULTS
  Recovery and analysis of live, islet-infiltrating T cells from the islets of cadaveric donors with T1D revealed a broad repertoire and proinflammatory phenotype of CD4 T-cell autoreactivity to peptide targets from islet proteins, including proinsulin, as well as CD4 T-cell reactivity to a number of post-translationally modified peptides, including peptides with citrullinations and hybrid insulin peptide fusions. Islet-infiltrating CD8 T cells were also derived and required further isolation and characterization.
  
  
  CONCLUSIONS
  The recovery of live, islet-infiltrating T cells from donors with T1D, reactive with a broad range of known targets and post-translationally modified peptides, allows for the specific functional analysis of islet-infiltrating T cells for the development of antigen-specific immunotherapies.
authors.affiliation: Division of Diabetes, Department of Medicine, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Sally C
authors.initials: SC
authors.lastname: Kent
authors.forename: Jenny Aurielle B
authors.initials: JA
authors.lastname: Babon
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity
chemical_list: D000941:Antigens; D007328:Insulin