Noel K. Maclaren

HERV-K10s and Immune-Mediated (Type 1) Diabetes

(A) HTDV/HERV-K particles expressed in human teratocarcinoma cells. Ultrathin section, (B) immunolabeling with goat anti HERV-K Gag antibody in ultrathin frozen section (right). Bar represents 250 nm

Molecular and Cellular Basis of Immune-Mediated (Type 1) Diabetes

Immune-mediated (type I) diabetes (IMD), a multifactorial autoimmune disease, is determined by both environmental and genetic factors (1). Lymphocytic infiltration of pancreatic islets (insulitis) is the hallmark of the disease (2,3). The infiltration of islets proceeds slowly and has most times been present for years before the clinical diagnosis (4–6). Studies suggest that the autoimmune process that leads to IMD often begins during the first few years of life (7,8). The inflammatory infiltrate of islets consists mostly of CD8+ T cells plus variable numbers of CD4+ T cells, B-lymphocytes, macrophages, and natural killer cells (3). Massive β cell destruction by infiltrating cells, however, could be a late event in the process, which results in symptomatic diabetes only when at least 80% of the volume of beta cells have been destroyed (3). The destruction is mainly mediated by T cells. However, it is accompanied by circulating marker, islet cell autoantibodies (ICA) to pancreatic β-cells proteins (9,10), which can be used to predict the disease.