J. Clin. Invest. https://doi.org/10.1172/JCI126595 (2019)

The rate of loss of beta cells in type 1 diabetes (T1D) can be highly variable between patients. In the Journal of Clinical Investigation, Long and colleagues use mass cytometry to deep-phenotype islet-specific CD8+ T cells from patients with T1D and healthy controls in order to understand whether these cells — which are known drivers of T1D — influence the rate of loss of residual beta cell mass. Patients with T1D were stratified into ‘slow’ or ‘rapid’ progressors depending on the rate of C-peptide loss. Interestingly, slow and rapid progressors and even healthy controls showed equivalent frequencies of islet-reactive CD8+ T cells in peripheral blood; however, the phenotype of the CD8+ T cells clearly differed. Specifically, slow progressors’ cells showed an exhausted phenotype and were poorly responsive in vitro, whereas rapid progressors’ CD8+ T cells had an activated phenotype. CD8+ T cell phenotype may thus represent a useful biomarker to predict the progression of T1D.