Pancreatic Islet Cell Hyperexpression
Pancreatic islet cell hyperexpression of HLA class-I was first observed from a small number of autopsy specimens from type 1 diabetes (T1D) patients in the 1980s, but in recent years, this notion was challenged as a potential artifact. Richardson et al. performed immunohistochemistery, immunofluorescence, and Affymetrix array analysis of RNA isolated from microdissected islets to deterimine HLA class-I expression levels in transplant quality pancreata from organ donors with T1D and control subjects without diabetes.
This study confirmed that all endocrine cell types within islets of T1D donors were characterized by significant hyperexpression of HLA-class I compared to control donor tissues. HLA-class I hyperexpression disproportionately affected insulin-containing islets and generally waned with disease duration, concurrent with the decline in residual insulin positive beta cell mass. HLA-class I hyperexpression, now considered a defining feature of T1D pathology, is a hallmark of islet inflammation that likely promotes insulitis and beta cell killing by autoreactive cytotoxic CD8+ T cells. Exposure to inflammatory cytokines and/or beta cell stress may drive upregulation of HLA-class I, but these finding underscore an important notion that beta cells indeed participate in their own demise.
Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes.
Richardson SJ, Rodriguez-Calvo T, Gerling IC, Mathews CE, Kaddis JS, Russell MA, Zeissler M, Leete P, Dahl-Jorgensen K, von Herrath M, Pugliese A, Atkinson M, Morgan NG (2016).