Autoreactive T cells in type 1 diabetes
Alberto Pugliese
Alberto Pugliese
Published August 1, 2017
Citation Information: J Clin Invest. 2017;127(8):2881-2891. https://doi.org/10.1172/JCI94549.
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Review

Autoreactive T cells in type 1 diabetes

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease that causes severe loss of pancreatic β cells. Autoreactive T cells are key mediators of β cell destruction. Studies of organ donors with T1D that have examined T cells in pancreas, the diabetogenic insulitis lesion, and lymphoid tissues have revealed a broad repertoire of target antigens and T cell receptor (TCR) usage, with initial evidence of public TCR sequences that are shared by individuals with T1D. Neoepitopes derived from post-translational modifications of native antigens are emerging as novel targets that are more likely to evade self-tolerance. Further studies will determine whether T cell responses to neoepitopes are major disease drivers that could impact prediction, prevention, and therapy. This Review provides an overview of recent progress in our knowledge of autoreactive T cells that has emerged from experimental and clinical research as well as pathology investigations.

Authors

Alberto Pugliese

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Figure 2

CD8+ T cell responses to pancreatic β cells.

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CD8+ T cell responses to pancreatic β cells. Schematic representation of...
Schematic representation of major autoantigen classes that may be targeted by CD8+ T cells, the predominant immune cell type in the insulitis. As described in the main text, these may include native antigens and neoepitopes. The generation of these epitopes may be promoted by β cell inflammation and stress. Insulitis is often associated with an interferon response with hyperexpression of HLA class I molecules, which may be induced by viral infections. Hyperexpression of HLA class I molecules facilitates presentation of autoantigen epitopes to CD8+ T cells. Whether islet-infiltrating CD8+ T cells also target viral epitopes remains to be investigated.