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Exhausted-like CD8 T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects - sorted CD8 subsets

ABSTRACT: Bulk RNA-sequencing of sorted CD8 T cell subsets from recent-onset T1D subjects treated with alefacept

ORGANISM(S): Homo sapiens

PROVIDER: GSE163731 | GEO | 2020/12/23

REPOSITORIES: GEO

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Exhausted-like CD8+ T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects.

Project description: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.

| S-EPMC7934874 | biostudies-literature

Distinct exhausted CD8 T cell populations are linked to C-peptide preservation in alefacept-treated, recent onset T1D subjects

Project description:Bulk RNA-sequencing of sorted CD8 T cells from recent-onset T1D subjects treated with alefacept.

2020-12-10 | GSE158292 | GEO

Exhausted-like CD8 T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects - sorted CD8 subsets

Project description:Exhausted-like CD8 T cell phenotypes linked to C-peptide preservation in alefacept-treated T1D subjects - sorted CD8 subsets

| PRJNA687381 | ENA

Distinct exhausted-like CD8 T cell populations are linked to C-peptide preservation in alefacept-treated, recent onset T1D subjects

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-23 | GSE163732 | GEO

Distinct exhausted CD8 T cell populations are linked to C-peptide preservation in alefacept-treated, recent onset T1D subjects

Project description:Distinct exhausted CD8 T cell populations are linked to C-peptide preservation in alefacept-treated, recent onset T1D subjects

| PRJNA664761 | ENA

Distinct exhausted-like CD8 T cell populations are linked to C-peptide preservation in alefacept-treated, recent onset T1D subjects

Project description:Distinct exhausted-like CD8 T cell populations are linked to C-peptide preservation in alefacept-treated, recent onset T1D subjects

| PRJNA687377 | ENA

A composite immune signature parallels disease progression across T1D subjects (RNA-Seq Cohort 2 Cell Sorted)

Project description:Peripheral blood mononuculear cells were thawed and sorted into B cell, CD4+ T cells, CD8+ T cells, and monocytes. Samples were obtained from control-arm subjects enrolled in 2 clinical trials evaluating immunotherapies in T1D that were conducted by the Immune Tolerance Network. The trials had similar study timepoints, clinical and metabolic measurements, and data and sample collection plans. Total RNA was isolated from the sorted cell populations and then RNAseq libraries were prepared.

2020-02-03 | GSE131527 | GEO

Next Generation Sequencing unveils the difference between human TR3-56 cells from healthy and T1D subjects

Project description:Purpose: The goal of this study was the transcriptome high-throughput data analysis of TR3-56 cells isolated from peripheral blood of healthy and T1D subjects Methods: total RNA profile of human TR3-56 cells from healthy and T1D subjects (1. Healthy Subject, 2.Healthy Subject, 3.Healthy Subject; 4. T1D subject, 5. T1D subject, 6. T1D subject; deeep sequencing, using Ovation SoLo RNA-seq Library Preparation KIt (NuGen), Library were prepared for sequencing on NextSeq 500 (llumina technology) Results: Principal component analysis and unsupervised clustering showed that TR3-56 cells from healthy donors are transcriptionally different from TR3-56 cells isolated from T1D subjects. Conclusions: Several genes are differently regulated between TR3-56 cells from T1D and healthy donors.

2020-02-18 | GSE134916 | GEO

A composite immune signature parallels disease progression across T1D subjects (Affymetrix Cohort 2)

Project description:We used an array-based bioassay whereby serum is used to induce transcription in healthy “reporter” leukocytes. Serum samples were obtained from control-arm subjects enrolled in 3 clinical trials evaluating immunotherapies in T1D that were conducted by the Immune Tolerance Network. The included trials evaluated immune-modifying therapy in new-onset T1D, with similar trial timecourses, primary outcomes, and data and sample collection. Total RNA was isolated from the reporter cell line for gene expression analysis.

2020-02-03 | GSE131524 | GEO

Interconnected lineage trajectories link conventional and NK-like exhausted CD8+ T cells beneficial in T1D [P452_3]

Project description:While distinct NK-like CD57+ and PD-1+ CD8+ exhausted T cell populations (Tex) were both linked to beneficial immunotherapy response in autoimmune Type 1 Diabetes (T1D) patients, relationships between these cell types are poorly understood. We show that PD-1+ and CD57+ Tex populations in this context were epigenetically similar, but CD57+ Tex cells displayed unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1+ and CD57+ Tex also showed reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57+ Tex showed unappreciated gene expression heterogeneity and shared clonal relationships with PD-1+ Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1+, Tex-CD57+, Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment.

2024-01-17 | GSE237613 | GEO

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