Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (microarray)

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. We used unbiased whole blood transcriptomic approaches to identify cellular and molecular markers that accompany successful treatment with a non-Fc binding anti-CD3 antibody (teplizumab)