Type 1 diabetes is characterized by recognition of one or more β-cell proteins by the immune system. The list of target antigens in this disease is ever increasing and it is conceivable that... Show moreType 1 diabetes is characterized by recognition of one or more β-cell proteins by the immune system. The list of target antigens in this disease is ever increasing and it is conceivable that additional islet autoantigens, possibly including pivotal β-cell targets, remain to be discovered. Many knowledge gaps remain with respect to the disorder's pathogenesis, including the cause of loss of tolerance to islet autoantigens and an explanation as to why targeting of proteins with a distribution of expression beyond β cells may result in selective β-cell destruction and type 1 diabetes. Yet, our knowledge of β-cell autoantigens has already led to translation into tissue-specific immune intervention strategies that are currently being assessed in clinical trials for their efficacy to halt or delay disease progression to type 1 diabetes, as well as to reverse type 1 diabetes. Here we will discuss recently gained insights into the identity, biology, structure, and presentation of islet antigens in relation to disease heterogeneity and β-cell destruction. Show less
The field of Type 1 diabetes research has been quick to embrace the era of translational medicine in the recent epoch. Building upon some 30 years of intense immunological research, the past decade... Show moreThe field of Type 1 diabetes research has been quick to embrace the era of translational medicine in the recent epoch. Building upon some 30 years of intense immunological research, the past decade has been marked by a series of clinical trials designed to evaluate the potential beneficial effects of a range of immune intervention and prevention strategies [1(••),2-5]. At the heart of Type 1 diabetes is an autoimmune process, the consequence of which is immune-mediated destruction of islet β-cells. Although understanding the pathogenesis of islet autoimmunity is critical, there are also good reasons to focus research onto the β-cell destructive process itself. Measuring preservation of function of insulin-producing cells is currently the best means available to evaluate potential beneficial effects of immunotherapy, but there is an urgent need to discover and monitor immunological correlates of this β-cell destructive process. Whilst the best approach to intervention and prevention has yet to emerge, it is logical that future attempts to intelligently design therapeutics for Type 1 diabetes will need to be predicated on a clear understanding of the process of β-cell destruction and the immune components involved. For these reasons, this review will focus on the role of diabetogenic T lymphocytes in this disease-defining event. Show less
