Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes.

ABSTRACT: Biologic treatment of T1D typically results in transient stabilization of C-peptide levels (a surrogate for endogenous insulin secretion) in some patients, followed by progression at the same rate as in untreated control groups. Here, we used integrated systems biology and flow cytometry approaches with clinical trial blood samples to elucidate pathways associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody teplizumab. We identified a population of CD8 T cells that accumulated in subjects with the best response to treatment (responders) and showed that these cells phenotypically resembled exhausted T cells by expressing high levels of the transcription factor EOMES, effector molecules, and multiple inhibitory receptors (IRs), including TIGIT a

SUBMITTER: Long SA 

PROVIDER: S-EPMC5486405 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature