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

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE158292 | GEO | 2020/12/10

REPOSITORIES: GEO

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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.

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

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

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

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

Project description: Not available

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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

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Expression data from recent-onset T1D patients and controls

2008-02-22 | GSE10586 | 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

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Transcription profiling of human FoxP3+CD4+CD25+high regulatory T cells (Tregs) isolated from recent-onset type 1 diabetes mellitus (T1D) patients and controls

Project description:Naturally occurring FoxP3+CD4+CD25+high regulatory T cells (Tregs) play an important role in dominant tolerance, suppressing auto-reactive CD4+CD25- T cell activity. Although Tregs from T1D subjects are functionally deficient, there is little knowledge of the molecular mechanisms that orchestrate this loss of Treg function. We observed increased apoptosis (by a novel YOPRO-1/7AAD dual staining protocol) and decreased suppression in polyclonal Tregs in the periphery from high at-risk and T1D subjects. We hypothesize that prior to and during the onset of disease, Tregs lack pro-survival signals and are caught up in a relatively deficient cytokine milieu whose effects may be detectable in the periphery. Microarray analysis was performed on un-stimulated Tregs from 12 subjects with newly diagnosed T1D and 15 healthy controls. Experiment Overall Design: Recent-onset T1D subjects were T1D patients diagnosed within 1 year. At the time of each visit, the following clinical measurements were taken: HbA1c, glucose level, height, weight and BMI. The presence of auto-antibodies was measured from peripheral blood. Peripheral blood mononuclear cells (PBMCs) were collected and Tregs were isolated using FACS isolation. RNA was isolated, amplified and cRNA was fragmented and hybridized to Affymetrix whole genome U133Plus2.0 arrays having 54675 probe-sets. Bayesian Hierarchical analysis (BGX) was used to analyze the data.

2008-04-07 | E-GEOD-10586 | biostudies-arrayexpress

Functional Genomics Analysis of Islets from Recent and Longstanding T1D Reveals the Need for Distinct Approaches to Therapy

Project description:Our current understanding of the pathogenesis of T1D arose in large part from studies using the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D). Of concern, therapeutic interventions shown to significantly dampen or even reverse disease in mouse models have not successfully translated into interventions in human T1D. The present study addresses this disconnect in research translation by directly analyzing human donor islets from individuals with T1D, aiming to provide insight into disease mechanisms and identify potential target pathways for therapeutic intervention. We obtained human islets from a young individual with short-duration T1D, an older individual with long-duration T1D and three non-diabetic donors, and performed unbiased functional genomic analysis by high depth RNA sequencing on these unique cases. This analysis identified several inflammatory pathways upregulated in short-duration disease, which surprisingly included many components of innate immunity. Subsequent manipulation of one of these pathways/factors in NOD mice resulted in a significant reduction in diabetes progression when inhibition occurred early in disease progression. Taken together our data demonstrates that the direct analysis of human islets is essential for identifying relevant and promising novel targets for translation into effective therapeutic interventions for human T1D.

2018-07-30 | GSE102371 | 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

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