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Title: Molecular plasticity of regulatory T cells in allogeneic stem cell transplantation      
dateReleased:
12-31-2010
description:
Graft-versus-host disease (GvHD) is still one of the major complications following allogeneic stem cell transplantation (SCT) triggered by alloreactive donor T cells. Whereas murine data have clearly shown the beneficial effects of regulatory T cells (Tregs) on the development of GvHD, data from the human system are rare mainly due to low cell numbers of circulating or organ-infiltrating Tregs in lymphopenic patients. Here, we present a comparative analysis of Tregs from patients with and without acute/ chronic GvHD designed as a dynamical approach studying the whole genome profile over the first 6 months after SCT. For this purpose, blood samples were collected monthly for FACS-based isolation of CD4+CD25highCD127low/- Tregs. The Treg transcriptome showed a high stability in the first half year representing the most sensitive time window for tolerance induction. However, the comparison of the Treg transcriptome from patients with and without GvHD uncovered regulated gene transcripts that point to a reduced suppressive function of Tregs with diminished migration capacity to the target organs likely contributing to the development of GvHD. These findings highlight the critical role of human Tregs in the pathophysiology of GvHD and identify novel targets for the manipulation of Tregs to optimize cellular immune intervention strategies. Keywords: cell type comparison Relative gene expressions were determined by normalized intensity values. GeneSpring analysis was performed using the Treg transcriptome data with following comparisons: no GvHD d90 versus no GvHD d150, no GvHD d90 versus acute GvHD, no GvHD d150 versus chronic GvHD, acute GvHD versus chronic GvHD, acute GvHD versus GvHD d90 and chronic GvHD versus GvHD d150 (Figure 2). Cut-off was a transcript fold change of 2 or -2 in at least one comparison. StudentĀ“s t-test was used to identify significant expression changes.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-23332
refinement:
raw
alternateIdentifiers:
23332
keywords:
functional genomics
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-AFFY-44
name:
Affymetrix GeneChip Human Genome U133 Plus 2.0 [HG-U133_Plus_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-23332/E-GEOD-23332.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-23332/E-GEOD-23332.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23332
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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