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

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

PROVIDER: PRJNA687381 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13292073.fastq.gz	Fastqsanger.gz
	SRR13292074.fastq.gz	Fastqsanger.gz
	SRR13292075.fastq.gz	Fastqsanger.gz
	SRR13292076.fastq.gz	Fastqsanger.gz
	SRR13292077.fastq.gz	Fastqsanger.gz

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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

2020-12-23 | GSE163731 | GEO

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

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

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-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

Transcription profiling of mouse naive, effector, memory and exhausted virus-specific CD8 T cells after chronic viral infection

Project description:CD8 T cells normally differentiate from resting naÃ¯ve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Experiment Overall Design: Three or four independent samples were sorted by flow cytometry for each cell type (naive, effector, memory and exhausted) virus-specific CD8 T cells. RNA was extracted and hybridized to Affymetrix microarrays.

2008-06-16 | E-GEOD-9650 | biostudies-arrayexpress

CD39 expression identifies terminally exhausted CD8+ T cells

Project description:Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion. CD8+ T cells from subjects with HCV infection were sorted and pelleted and re-suspended in TRIzol (Invitrogen). RNA extraction was performed using the RNAdvance Tissue Isolation kit (Agencourt). Concentrations of total RNA were determined with a Nanodrop spectrophotometer or Ribogreen RNA quantification kits (Molecular Probes/Invitrogen). RNA purity was determined by Bioanalyzer 2100 traces (Agilent Technologies). Total RNA was amplified with the WT-Ovation Pico RNA Amplification system (NuGEN) according to the manufacturer's instructions. After fragmentation and biotinylation, cDNA was hybridized to HG-U133A 2.0 microarrays (Affymetrix).

2015-09-08 | E-GEOD-72752 | biostudies-arrayexpress

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

Project description:Interconnected lineage trajectories link conventional and NK-like exhausted CD8+ T cells beneficial in T1D

| PRJNA996033 | ENA

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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