Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (microarray)

ABSTRACT: Biologic agents active in other autoimmune settings have had variable effectiveness in newly diagnosed type 1 diabetes (T1D) where treatment across therapeutic targets is accompanied by transient stabilization of C-peptide levels in some patients, followed by progression at the same rate as in control groups. Why disparate treatments lead to similar clinical courses is currently unknown. Here, we use integrated systems biology and flow cytometry approaches to elucidate immunologic mechanisms associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody, teplizumab.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84934 | GEO | 2016/12/06

SECONDARY ACCESSION(S): PRJNA335704

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (whole blood RNA-seq)

Project description:Biologic agents active in other autoimmune settings have had variable effectiveness in newly diagnosed type 1 diabetes (T1D) where treatment across therapeutic targets is accompanied by transient stabilization of C-peptide levels in some patients, followed by progression at the same rate as in control groups. Why disparate treatments lead to similar clinical courses is currently unknown. Here, we use integrated systems biology and flow cytometry approaches to elucidate immunologic mechanisms associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody, teplizumab. This work is part of the Immune Tolerance Network AbATE study (Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes); data are also available through the ITN TrialShare portal: https://www.itntrialshare.org/project/Studies/ITN027AIDB/Study%20Data/begin.view?.

2016-11-21 | GSE85531 | GEO

Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (bulk RNA-seq of sorted CD8+ T-cells)

2016-11-21 | GSE85530 | GEO

Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes (single-cell RNA-seq of sorted CD8+ T-cells)

2016-12-06 | GSE85527 | GEO

Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes

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

2016-11-21 | GSE85573 | GEO

Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes

Project description:Partially exhausted CD8+ T cells are associated with clinically beneficial response to Teplizumab in new onset type I diabetes

| PRJNA338813 | ENA

Microarray analysis of the migrating human CD4+ T cell population from the spleen of humanized mice in response to treatment with Teplizumab or hIg

Project description:In order to identify genes expressed by cells that leave the spleen, the spleens were harvested from untreated reconstituted humanized mice (N=4) and a single cell suspension was prepared . The cultures were treated with either teplizumab (anti human CD3 hOKT3g1(Ala-Ala)) or hIg for 18 hrs in vitro. Splenocytes were also harvested 18 hrs after reconstituted mice (N=4) were treated with teplizumab in vivo. The humanized mice used where NOD/SCID IL2gc-/- (NSG) reconstituted with human CD34+ at birth. Total RNA was obtained form sorted human CD4 splenocytes 18 hours post treatment. Comparsons were made between the treatment groups.

2012-02-27 | E-GEOD-34163 | biostudies-arrayexpress

Microarray analysis of the migrating human CD4+ T cell population from the spleen of humanized mice in response to treatment with Teplizumab or hIg

2012-02-27 | GSE34163 | 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

Interconnected lineage trajectories link conventional and NK-like exhausted CD8+ T cells beneficial in T1D [P362-1]

2024-01-17 | GSE237611 | GEO

Eliane_IL2.Rapa bis

Project description:Administration of low-dose IL-2 prevents and cures type 1 diabetes (T1D) in NOD mice by boosting pancreatic regulatory T cells (Tregs) and is currently being evaluated in humans. Here, to improve treatment efficacy we tested higher IL-2 doses that, despite further boosting Tregs, rapidly precipitated T1D in pre-diabetic mice due to generalized immune activation. Although the combination of rapamycin (RAPA) plus IL-2 prevents NOD T1D development, a recent clinical trial translating this strategy into patients was halted due to C-peptide decline. Here, we show that RAPA/IL-2 combination was also ineffective to cure new onset T1D in mice and, surprisingly, RAPA broke IL-2-induced tolerance in a reversible way. RAPA partially counteracted IL-2 effects on Tregs and the combined treatment unexpectedly, impaired glucose homeostasis at multiple levels, possibly explaining the clinical outcome. Our data help understand IL-2 alone or RAPA/IL-2 combination limitations and could lead to the design of improved T1D therapies.

2013-12-10 | E-MEXP-3789 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data