Epitope specific T cells in type 1 diabetes: From detection to immunotherapy

Monitoring autoreactive T cells, directed towards immunodominant epitopes is useful in assessment of disease progression and distinguishing different forms of autoimmune diabetes. In a recent work, the authors reported that individuals with slower progression of autoimmune diabetes, i.e. latent autoimmune diabetes in adults (LADA) harbour lower frequency of preproinsulin (PPI) specific CD8+ T cells compared to those with typical type 1 diabetes (T1D). Further, the PPI specific CD8+ T cells of T1D subjects showed higher proliferation potential and greater proportion of cells with effector phenotype. Besides highlighting the differences in the repertoire of PPI specific peripheral CD8+ T cells between T1D and LADA subjects, this study also demonstrates that autoreactive CD8+ T cells directed towards immunodominant epitopes persist over a period of time in these subjects and hence present as attractive targets for immunotherapy. Generating epitope specific CD4+ regulatory T cells (Tregs) directed towards the same antigen can counter regulate effector CD4+ T cells and further limit the frequency and actions of such autoreactive CD8+ T cells.Recent animal studies have indeed shown that islet antigen specific Tregs can in fact reverse autoimmune diabetes by targeting T cells that infiltrate pancreas. Therefore, combining the approaches of identification of epitope specific T cells using MHC multimers and Treg specific markers, can facilitate the scope of epitope specific immunotherapy in human T1D.