CD8+ T-cells and their interaction with other cells in damage to islet β-cells

The autoimmune attack on pancreatic β-cells is orchestrated by a variety of cells that produce cytokines and other toxic mediators. CD8+ T-cells work together with other lymphocytes and antigen-presenting cells to mediate this damage and have been shown in animal models to be important both in the early stages of diabetes development and in the final effector stages. Recently, there has also been much interest in studying CD8+ T-cells that may play a role in human Type 1 diabetes and identifying their antigenic targets. The present paper will focus on the activation of CD8+ T-cells and their interaction with other cells of the immune system and discuss the target antigens and mechanisms of damage that the CD8+ T-cells use in the attack on the islet β-cell. Introduction Damage to pancreatic β-cells in Type 1 diabetes occurs through a variety of mechanisms that include CD8+ T-cellular cytotoxic damage and cytokines. The cellular infiltrate within the islets consists of a number of cell types including CD8+ Tcells, CD4+ T-cells, B-cells, macrophages and dendritic cells. In studying the immunology of Type 1 diabetes, there has been considerable interest in which cells cause damage and what they recognize, the cytotoxic mediators produced, how the immune cells damage the islet β-cells and how these cells may be controlled. Ultimately, the hope in understanding these factors is to identify pathways that may be amenable to intervention to prevent the damage to the islets. Why are CD8+ T-cells important? Many studies carried out in the NOD (non-obese diabetic) mouse model of Type 1 diabetes have indicated that CD8+ T-cells inflict islet β-cell damage both at an early stage in diabetes development and at the final effector phase [1–3]. Although there is less direct evidence in humans about the early phases of disease, at the time of diagnosis of diabetes, in biopsies of the pancreas, a significant proportion of the infiltrating cells are CD8+ T-cells [4]. Furthermore, in postmortem samples of Type 1 diabetes patients, CD8+ T-cells are also present within the islets [5]. There is clearly development of CD8+ T-cell memory against islet autoantigens, as shown by the recurrence of diabetes in identical twins, one of whom had received half a pancreas from their non-diabetic twin,