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.