Chapter 4 CD8+ T Cells in Type 1 Diabetes

Abstract

Type 1 diabetes (T1D), an autoimmune disease once thought to be mediated exclusively by beta cell-specific CD4+ T cells, is now recognized as one in which autoreactive CD8+ T cells play a fundamental role. In the nonobese diabetic (NOD) mouse model, CD8+ T effector cells take centre stage in the destruction of pancreatic beta cells and contribute to sustaining islet inflammation. Recent investigations have elucidated the mechanisms underlying the activation, homing, and beta cell destructive properties of this type of cells. Another important area is the development and testing of novel preemptive or therapeutic "vaccines" that, by targeting effector and/or regulatory autoreactive CD8+ T cell specificities may be able to induce immunological tolerance to beta cells. In humans, our understanding of the role of CD8+ T cells in T1D is also growing, through genetic linkage analyses, as well as epitope identification and characterization of disease-relevant CD8+ T cell responses in patient blood samples. The following review discusses these important advances and how they can converge towards the goal of developing an antigen-specific immunotherapy for T1D.