In Situ Characterization of Autoimmune Phenomena and Expression of HLA Molecules in the Pancreas in Diabetic Insulitis

TLDR

Monoclonal antibodies were employed postmortem to identify pancreatic infiltrating cells in a 12‑year‑old with newly diagnosed insulin‑dependent diabetes. The pancreatic infiltrate was dominated by cytotoxic/suppressor T cells, with additional activated T cells (HLA‑DR⁺/IL‑2R⁺), scattered IgG‑positive immune cells, complement‑fixing IgG deposits, upregulated Class I HLA on islet cells, HLA‑DR⁺ beta cells, and dilated, HLA‑DR⁺ capillary endothelium, all suggesting a sequence of events contributing to beta‑cell destruction in type I diabetes. Published in N Engl J Med 1985; 313:353.

Abstract

After the death of a 12-year old girl with newly discovered insulin-dependent diabetes mellitus, we used monoclonal antibodies in an effort to identify the cells invading the pancreas. The majority of infiltrating lymphocytes were of the T cytotoxic/suppressor phenotype, but other T-cell subpopulations were present. Some of the T cells were "activated" (positive for HLA-DR antigen, and the interleukin-2 receptor). Immunocytes bearing IgG were scattered in the gland, and complement-fixing IgG antibodies were deposited in some islets. Increased expression of Class I (HLA-A, B, and C) molecules was observed in the affected islet cells, and in damaged islets showing scant lymphocytic infiltration, some beta cells (still producing insulin), but not glucagon or somatostatin cells, were HLA-DR positive. The capillary endothelium was markedly dilated and strongly HLA-DR positive. These findings may contribute to an understanding of the sequence of events leading to the destruction of beta cells in classic Type I diabetes mellitus. (N Engl J Med 1985; 313:353)