ArticleScience immunology2016
Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes.
Article in Science immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
169 citing papers in PubMed, 1 synthesis or guideline pooled it, 241 citations in OpenAlex.
- Pediatric Endocrine Society Statement on Considerations for Use of Teplizumab (Tzield™) in Clinical Practice.Hormone research in paediatrics · 2025Guideline
- Safety and efficacy of human gingiva-derived mesenchymal stem cells in patients with type 1 diabetes: a double-blind, randomized, placebo-controlled, phase 1 trial.Signal transduction and targeted therapy · 2026Trial
- Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab.Diabetologia · 2025Trial
- Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes.The Journal of clinical investigation · 2024Trial
- Trial
- Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis.JCI insight · 2022Trial
- Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals.Science translational medicine · 2021Trial
- Exhausted-like CD8+ T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects.JCI insight · 2021Trial
- A randomised, single-blind, placebo-controlled, dose-finding safety and tolerability study of the anti-CD3 monoclonal antibody otelixizumab in new-onset type 1 diabetes.Diabetologia · 2021Trial
- Effects of probiotic administration on immune responses of children and adolescents with type 1 diabetes to a quadrivalent inactivated influenza vaccine.Human vaccines & immunotherapeutics · 2020Trial
- Immunomodulatory activity of humanized anti-IL-7R monoclonal antibody RN168 in subjects with type 1 diabetes.JCI insight · 2019Trial
- An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.The New England journal of medicine · 2019Trial
- Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti-CD3ε mAb in new-onset type 1 diabetes mellitus patients.British journal of clinical pharmacology · 2019Trial
- Elevated T cell levels in peripheral blood predict poor clinical response following rituximab treatment in new-onset type 1 diabetes.Genes and immunity · 2019Trial
- Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbADiabetes care · 2018Trial
- Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes.The Journal of clinical investigation · 2018Trial
- Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes.Cellular immunology · 2017Trial
- Going to the source: pancreatic lymph nodes maintain stem-like CD8+ T cells in human type 1 diabetes.The Journal of clinical investigation · 2026Article
- Immune dysregulation and stem-like CD8+ T cell enrichment in type 1 diabetes pancreatic lymph nodes.The Journal of clinical investigation · 2026Article
- Considerations for the clinical use of teplizumab in stage 2 Type 1 diabetes: A Consensus Statement from the British Society of Paediatric Endocrinology and Diabetes (BSPED) and the Association of British Clinical Diabetologists (ABCD).Diabetic medicine : a journal of the British Diabetic Association · 2026Article
109 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
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 and KLRG1. These cells expanded after treatment, with levels peaking after 3-6 months. To functionally characterize these exhausted-like T cells, we isolated memory CD8 TIGIT+KLRG1+ T cells from responders and showed that they exhibited expanded TCR clonotypes, indicative of prior in vivo expansion; recognized a broad-based spectrum expressed of environmental and auto-antigens; and were hypo-proliferative during polyclonal stimulation, increasing expression of IR genes and decreasing cell cycle genes. Triggering these cells with a recombinant ligand for TIGIT during polyclonal stimulation further downregulated their activation, demonstrating their exhausted phenotype was not terminal. These findings identify and functionally characterize a partially exhausted cell type associated with response to teplizumab therapy and suggest that pathways regulating T cell exhaustion may play a role in successful immune interventions for T1D.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.