Measurement of CD8+ T Cell Responses in Human Type 1 Diabetes

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Abstract
Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease targeting pancreatic beta-cells. Despite this textbook definition, it is quite striking that neither the diagnosis nor the therapy nor the follow-up of T1D "belong" to immunologists, but rather to endocrinologists whose only option is to limit the consequences of the disease. Immune therapies would seem better suited to correct the causes of T1D, but critical laboratory tools are missing for early diagnosis, prognostic stratification, and therapeutic follow-up. The immune markers routinely available are limited to autoantibodies, which have some intrinsic limitations. Because T cells are central pathogenic actors of T1D, the quest for their measurement appeared to offer a path towards new autoimmune markers. Given the strong association between T1D susceptibility and the HLA class II locus, investigators have long been focused on CD4(+) T cells. However, data gathered in the NOD mouse and the examination of human insulitis point to a critical role of CD8(+) T cells in the pathogenesis of T1D. These observations have revived interest in trying to measure CD8(+) T cell responses in human T1D. Achievement of this goal mainly depends on two factors. First, the relevant epitopes need to be identified. Second, appropriate readouts and measurement techniques need to be selected. This review summarizes recent advances on both of these battlefronts, and discusses the potential clinical applications of T cell assays.