Trial reportJCI insight2021
Exhausted-like CD8+ T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects.
Trial report in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
49 citing papers in PubMed, 69 citations in OpenAlex.
- 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
- Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis.JCI insight · 2022Trial
- 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
- Taming autoimmunity: Alpha-1 antitrypsin overexpressing mesenchymal stromal cells promote regulatory T cell crosstalk to reverse diabetes.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Beta cell-targeted PD-1 agonist inhibits cell-mediated autoimmunity in pancreas tissue slices.Science advances · 2026Article
- Aberrant immune regulation and enrichment of stem-like CD8bioRxiv : the preprint server for biology · 2026Article
- Article
- Can we cure autoimmunity?Current opinion in immunology · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Modulating immune response for the prevention and treatment of type 1 diabetes.Frontiers in immunology · 2026Review
- Inhibition of cell-mediated immunity in type 1 diabetes by beta cell-targeted PD-1 agonists in pancreas tissue slices.bioRxiv : the preprint server for biology · 2025Article
- Second generation CD2-targeting LFA-3 fusion protein SBT115301 to restore immune homeostasis in autoimmune disease.iScience · 2025Article
- Immunosuppressive agents in diabetes treatment: Hope or despair?World journal of diabetes · 2025Review
- Article
- Article
- Immunotherapies for prevention and treatment of type 1 diabetes.Immunotherapy · 2025Review
- Early expansion of TIGIT+PD1+ effector memory CD4 T cells via agonistic effect of alefacept in new-onset type 1 diabetes.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Immunotherapy-Based Strategies for Treatment of Type 1 Diabetes.Hormone research in paediatrics · 2025Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Clinical trials of biologic therapies in type 1 diabetes (T1D) aim to mitigate autoimmune destruction of pancreatic β cells through immune perturbation and serve as resources to elucidate immunological mechanisms in health and disease. In the T1DAL trial of alefacept (LFA3-Ig) in recent-onset T1D, endogenous insulin production was preserved in 30% of subjects for 2 years after therapy. Given our previous findings linking exhausted-like CD8+ T cells to beneficial response in T1D trials, we applied unbiased analyses to sorted CD8+ T cells to evaluate their potential role in T1DAL. Using RNA sequencing, we found that greater insulin C-peptide preservation was associated with a module of activation- and exhaustion-associated genes. This signature was dissected into 2 CD8 memory phenotypes through correlation with cytometry data. These cells were hypoproliferative, shared expanded rearranged TCR junctions, and expressed exhaustion-associated markers including TIGIT and KLRG1. The 2 phenotypes could be distinguished by reciprocal expression of CD8+ T and NK cell markers (GZMB, CD57, and inhibitory killer cell immunoglobulin-like receptor [iKIR] genes), versus T cell activation and differentiation markers (PD-1 and CD28). These findings support previous evidence linking exhausted-like CD8+ T cells to successful immune interventions for T1D, while suggesting that multiple inhibitory mechanisms can promote this beneficial cell state.
Indexed as
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.