The role of T lymphocytes in the pathogenesis of autoimmune type 1 diabetes: Implications for potential virus-mediated pathways

Evidence accumulated in the last 25 years, since the earliest characterizations of the cellular infiltrate in the pancreas in new-onset type 1 diabetes (Bottazzo et al. 1985), has led to a consensus view that type 1 diabetes (T1D) is an organ-specific autoimmune disorder in which T lymphocytes are critically involved in the process of b-cell death (Table 26.4). In the setting of a dysregulated immune system, b-cells in the pancreatic islets of Langerhans are destroyed, through a combination of targeting by autoreactive T lymphocytes and the local inflammatory milieu. The limited disease concordance in genetically identical twins (Redondo et al. 2008) implicates a complex interplay between host genetic and environmental factors in the initiation and perpetuation of islet inflammation. The possibility that viruses influence these events is the subject of this book. In this chapter the autoimmune pathways to b-cell damage are reprised, providing a knowledge-base upon which to build hypotheses and predictions in relation to a viral etiology for type 1 diabetes. The aim is to document the key immune cells involved, as well as the critical points at which pathways to disease are initiated. The potential role of viruses at these nodal points can then be highlighted as a means of discussing the key experiments that will enable progress in the field of the viral etiology of type 1 diabetes.