Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deconvoluting alloimmunity in time and space through Serial Intravascular Staining: Evidence for rapid donor tissue-resident memory T cell resident memory formation during gastrointestinal GVHD.

ABSTRACT: Here we have applied Serial Intravascular Staining (‘SIVS’), complemented by single cell transcriptomic analysis, to ascertain the time-, tissue- and donor-dependence of T cell infiltration-mediated immune pathology during aGVHD in a non-human primate (NHP) model. We demonstrate rapid differentiation of donor tissue-infiltrating CD8 T cells in situ into tissue-resident memory T cells (TRM), coincident with destruction of aGVHD target tissues. We also combined SIVS with single cell RNA Sequencing (scRNASeq) to identify the transcriptional programs controlling these actively infiltrating cells.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE142483 | GEO | 2020/07/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Deconvoluting alloimmunity in time and space through Serial Intravascular Staining: Evidence for rapid donor tissue-resident memory T cell resident memory formation during gastrointestinal GVHD.

Project description:Deconvoluting alloimmunity in time and space through Serial Intravascular Staining: Evidence for rapid donor tissue-resident memory T cell resident memory formation during gastrointestinal GVHD.

| PRJNA597145 | ENA

Spatiotemporal single-cell profiling of gastrointestinal GVHD reveals invasive and tissue-resident memory T cell states

Project description:One of the major barriers to understanding the control of T cell infiltration into target tissues has been the inherent difficulty in capturing the key variable of time in this process. Time is a critical variable, given that T cells are actively homing towards and infiltrating into target organs, and are concordantly evolving a highly pathogenic transcriptional program. Without understanding the time-dependency of T cell infiltration, we cannot fully comprehend key drivers and their dynamics. Here, we have been able to deconvolute time as a variable during T cell infiltration and tissue destruction during primate aGVHD by applying Serial Intravascular Staining (‘SIVS’) and pairing this with multiparameter flow cytotmetric and single-cell transcriptomic analysis. We also demonstrate significant overlap between NHP transcriptional signatures and those found in patients with active aGVHD, underscoring the clinical relevance of these findings.

2020-09-02 | GSE157280 | GEO

Generation and persistence of human tissue-resident memory T cells in lung transplantation

Project description:Tissue resident memory T cells (TRM) maintain immunity in diverse sites as determined in mouse models, while their establishment and role in human tissues has been difficult to assess. Here, we investigated human lung TRM generation, maintenance and function in airway samples obtained longitudinally from HLA-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of TRM signature markers including CD69, CD103, and CD49a, while lung-infiltrating recipient T cells gradually acquire TRM phenotypes over months in vivo. Single cell transcriptome profiling of airway T cells reveals that donor T cells comprise two TRM-like subsets with varying levels of expression of TRM-associated genes while recipient T cells comprised non-TRM and similar TRM-like subpopulations, suggesting de novo TRM generation. Transplant recipients exhibiting higher frequencies of persisting donor TRM experienced fewer adverse clinical events such as primary graft dysfunction and acute cellular rejection compared to recipients with low donor TRM persistence, suggesting that monitoring TRM dynamics could be clinically informative. Together, our results provide novel spatial and temporal insights into how human TRM develop, function, persist, and impact tissue integrity within the complexities of lung transplantation.

2019-04-03 | GSE124675 | GEO

Transcription profiling of human leukocytes from peripheral blood stem cell transplant patients to investigate acute graft versus host disease aGVHD

Project description:Allogeneic peripheral blood stem cell transplantation (PBSCT) is indicated for the treatment of high-risk hematological malignancies, and in some cases is a cancer cure. A major complication associated with PBSCT (affecting approximately half of recipients) is acute graft-versus-host disease (aGVHD). In aGVHD, alloreactive donor T cells becoming activated by host dendritic cells (DC) in response to pro-inflammatory cytokines released during the conditioning regimen. The result is donor-derived CD4+ T helper-type 1 (Th1) cells maturing and subsequently imposing cytolytic effector responses on host tissues, resulting in multi-organ damage. Despite this well-defined pathophysiological mechanism, there are no definitive markers for predicting aGVHD development or progression to clinically advanced stages. In the current study, we enrolled 8 PBSCT recipients in an IRB-approved study and collected peripheral blood at the time to engraftment. Of these, four patients developed aGVHD within 5-10 days post transplant. The remaining four patients were aGVHD-free. Using total RNA collected from whole blood leukocytes, we analyzed each recipientâs gene expression profile on Affymetrix GeneChip Human Genome U133 Plus 2.0 microarrays. Experiment Overall Design: Samples 1-4 are control patients; 5-8 are aGVHD patients. Peripheral blood was collected at engraftment and used for microarray analysis. In analysing the data, the type of transplant (MUD, related) was used as a covariate to assess if there were significant changes in gene expression between the control (1-4) and aGVHD (5-8) groups, based on a 10% FDR with a pooled error estimate.

2008-06-15 | E-GEOD-7510 | biostudies-arrayexpress

Transcriptome Profiling in tissues and blood from NHP-HCT Recipients

Project description:Tissue-specific T cell immune responses play a critical role in maintaining organ health, but can also drive immune pathology during both auto- and alloimmunity. The mechanisms controlling intra-tissue T cell programming remain unclear. Here, we leverage a non-human primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HCT) to probe the biological underpinnings of tissue-specific alloimmune disease, using a comprehensive systems immunology approach.Transcriptional profiling revealed substantial biological differences between T cells, infiltrating the lung and liver during aGVHD.

2025-01-01 | GSE283413 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptomes of aGVHD mice tranferred Wild Type or OTUD1-/- cells.

Project description:Donor OTUD1 deficiency significanltly ameliorates the severity of aGVHD mice. We used single cell RNA sequencing (scRNA-seq) to analyze the immune cells in aGVHD mice transferred wild type or OTUD1-deficient cells.

2022-12-16 | GSE212162 | GEO

Galectin-3 expression in donor T cells reduces GvHD severity and lethality after allogeneic hematopoietic cell transplantation

Project description:Abundant donor cytotoxic T cells that attack normal host organs remain a major problem for patients receiving allogeneic hematopoietic cell transplantation (Allo-HCT). Despite an increase in our knowledge of the pathobiology of acute graft versus host disease (aGvHD), the mechanisms regulating the proliferation and function of donor T cells remain unclear. Here, we show that activated donor T cells express galectin-3 (Gal-3) after allo-HCT. In both major and minor histocompatibility–mismatched models of murine aGvHD, expression of Gal-3 is associated with decreased T cell activation and suppression of the secretion of effector cytokines including IFN-γ and GM-CSF. Mechanistically, Gal-3 results in activation of NFAT signaling which can induce T cell exhaustion. Gal-3 overexpression in human T cells prevents severe disease by suppressing cytotoxic T cells in xenogeneic aGvHD models. Together these data identify the Gal-3-dependent regulatory pathway in donor T cells as a critical component of inflammation in aGvHD.

2023-03-13 | GSE225756 | GEO

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets II

Project description:Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating these two CD8+ populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft and lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103- TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.

2020-12-05 | GSE162686 | GEO

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets I

2020-12-05 | GSE162685 | GEO

Deciphering decidual leukocyte traffic with serial intravascular staining.

Project description:The decidual immunome is dynamic, dramatically changing its composition across gestation. Early pregnancy is dominated by decidual NK cells, with a shift towards T cells later in pregnancy. However, the degree, timing, and subset-specific nature of leukocyte traffic between the decidua and systemic circulation during gestation remains poorly understood. Herein, we employed intravascular staining in pregnant C57BL/6J mice and cynomolgus macaques (Macaca fascicularis) to examine leukocyte traffic into the decidual basalis during pregnancy. Timed-mated or virgin mice were tail-vein injected with labelled αCD45 antibodies 24 hours and 5 minutes before sacrifice. Pregnant cynomolgus macaques (GD155) were infused with labelled αCD45 at 2 hours or 5 mins before necropsy. Decidual cells were isolated and resulting suspensions analyzed by flow cytometry. We found that the proportion of intravascular (IVAs)-negative leukocytes (cells labeled by the 24h infusion of αCD45 or unlabeled) decreased across murine gestation while recent immigrants (24h label only) increased in mid- to late-gestation. In the cynomolgus model our data confirmed differential labeling of decidual leukocytes by the infused antibody, with the 5 min infused animal having a higher proportion of IVAs+ cells compared to the 2hr infused animal. Decidual tissue sections from both macaques showed the presence of intravascularly labeled cells, either in proximity to blood vessels (5min infused animal) or deeper into decidual stroma (2hr infused animal). These results demonstrate the value of serial intravascular staining as a sensitive tool for defining decidual leukocyte traffic during pregnancy.

| S-EPMC10806228 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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