title: CD4+T cell-dominant insulitis in acute-onset Type 1 diabetes mellitus associated with intraductal papillary mucinous adenoma.
abstract: The loss of insulin-producing pancreatic β-cells in Type 1 diabetes mellitus (DM) is presumably the result of a T cell-mediated process. In general, CD8+T cells are the predominant lymphocytes in the insulitis lesions, and CD4+T cell-dominant insulitis is very rare. We present a case of a 72-year-old woman presented with excessive thirst and a 3-month history of weight loss. She was in a state of ketosis, and her plasma glucose concentration and HbA1c value were elevated. Moreover, anti-islet autoantibodies were positive, thus acute-onset Type 1 DM was diagnosed. At the time of diagnosis, a tumour was detected in the pancreas; total pancreatectomy was carried out 2 months later. The pathological diagnosis was intraductal papillary mucinous adenoma. Immunohistochemical staining of a sample of non-tumorous pancreatic tissue revealed 13 insulitis lesions infiltrated by both CD4+and CD8+T cells, and interestingly there were more CD4+T cells than CD8+T cells in the lesions. Moreover, B cells and macrophages had also infiltrated the lesions, and these two cell frequencies were both positively correlated with CD4+as well as CD8+T cell frequencies. This was a rare case with acute-onset Type 1 DM characterized by CD4+T cell-dominant insulitis. Proinflammatory cytokines that can promote β-cell apoptosis or CD8+T cell function are reported to be secreted from CD4+T cells. Thus, together with B cells and macrophages, CD4+T cell-associated immune responses may have, directly and/or indirectly, played a role in the pathogenesis of the Type 1 DM in this patient.
authors.affiliation: Department of Internal Medicine, Federation of National Public Service Personnel Mutual Aid Associations, Tachikawa Hospital, Tachikawa 190-8531, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yajima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ogata
authors.forename: Akinori
authors.initials: A
authors.lastname: Hashiguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000150:complications* / Q000276:immunology; D017668:Age of Onset; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000150:complications* / Q000276:immunology; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000276:immunology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000172:deficiency; D007515:Islets of Langerhans / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000150:complications* / Q000276:immunology
chemical_list: D001323:Autoantibodies; D007328:Insulin