Sefina Arif1, Irma Pujol-Autonell1,2, Martin Eichmann1,3. 1. Peter Gorer Department of Immunobiology, Faculty of Life Sciences & Medicine, King's College London. 2. Biomedical Research Centre at Guy's and St Thomas' Hospitals and King's College London, London, UK. 3. Current address: Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
Abstract
PURPOSE OF REVIEW: The role of T cells specific for islet autoantigens is proven in pathogenesis of type 1 diabetes. Recently, there has been rapid expansion in the number of T-cell subsets identified, this has coincided with an increase in the repertoire of reported islet antigens mainly through the discovery of novel epitopes. A discussion of how these marry together is now warranted and timely. RECENT FINDINGS: In this review, we will discuss the autoreactivity against neo-epitopes. We then explore the growing array of T-cell subsets for both CD4 T cells, including follicular and peripheral T helper cells, and CD8 T cells, discussing evolution from naïve to exhausted phenotypes. Finally, we detail how subsets correlate with disease stage and loss of β-cell function and are impacted by immunotherapy. SUMMARY: The expanding list of T-cell subsets may be potentially encouraging in terms of elucidating disease mechanisms and have a role as biomarkers for disease progression. Furthermore, T-cell subsets can be used in stratifying patients for clinical trials and for monitoring immunotherapy outcomes. However, the definition of subsets needs to be refined in order to ensure that there is a uniform approach in designating T-cell subset attributes that is globally applied.
PURPOSE OF REVIEW: The role of T cells specific for islet autoantigens is proven in pathogenesis of type 1 diabetes. Recently, there has been rapid expansion in the number of T-cell subsets identified, this has coincided with an increase in the repertoire of reported islet antigens mainly through the discovery of novel epitopes. A discussion of how these marry together is now warranted and timely. RECENT FINDINGS: In this review, we will discuss the autoreactivity against neo-epitopes. We then explore the growing array of T-cell subsets for both CD4 T cells, including follicular and peripheral T helper cells, and CD8 T cells, discussing evolution from naïve to exhausted phenotypes. Finally, we detail how subsets correlate with disease stage and loss of β-cell function and are impacted by immunotherapy. SUMMARY: The expanding list of T-cell subsets may be potentially encouraging in terms of elucidating disease mechanisms and have a role as biomarkers for disease progression. Furthermore, T-cell subsets can be used in stratifying patients for clinical trials and for monitoring immunotherapy outcomes. However, the definition of subsets needs to be refined in order to ensure that there is a uniform approach in designating T-cell subset attributes that is globally applied.