Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (single-cell RNA-seq of sorted CD8+ T-cells). Homo sapiens

Biologic agents active in other autoimmune settings have had variable effectiveness in newly diagnosed type 1 diabetes (T1D) where treatment across therapeutic targets is accompanied by transient stabilization of C-peptide levels in some patients, followed by progression at the same rate as in control groups. Why disparate treatments lead to similar clinical courses is currently unknown. Here, we use integrated systems biology and flow cytometry approaches to elucidate immunologic mechanisms associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody, teplizumab. This work is part of the Immune Tolerance Network AbATE study (Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes); data are also available through the ITN TrialShare portal: https://www.itntrialshare.org/project/Studies/ITN027AIDB/Study%20Data/begin.view?. Overall design: We performed single-cell RNA-seq on 219 captured and sorted CD8+ T-cells from 3 responders at visit month 6 (N = 87, 75, 57); we sorted cells with and without EOMES-associated inhibitory receptors (TIGIT, KLRG1)); prior to RNA extraction, cells were stimulated with anti-CD3 and anti-CD28.