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Murine regulatory T cells stimulated by death receptor 3 agonistic antibody

ABSTRACT: CD4+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft and host disease (GVHD) in murine models of allogeneic hematopoietic cell transplantation. It was reported that a single treatment of the agonistic antibody to Death receptor 3 (DR3) in donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated. We analyzed the gene expression profile, immune phenotype, and function of DR3-activated Treg in a murine model of allogeneic hematopoietic cell transplantation.

ORGANISM(S): Mus musculus

PROVIDER: GSE83743 | GEO | 2016/06/28

SECONDARY ACCESSION(S): PRJNA326912

REPOSITORIES: GEO

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Murine regulatory T cells stimulated by death receptor 3 agonistic antibody

Project description:CD4+Foxp3+ regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft and host disease (GVHD) in murine models of allogeneic hematopoietic cell transplantation. It was reported that a single treatment of the agonistic antibody to Death receptor 3 (DR3) in donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated. We analyzed the gene expression profile, immune phenotype, and function of DR3-activated Treg in a murine model of allogeneic hematopoietic cell transplantation. CD4+Foxp3+ Treg were sorted from the mice stimulated with anti-DR3 or control antibody using fluorescence-activated cell sorter for RNA extraction and hybridization on Affymetrix microarrays.

2016-06-28 | E-GEOD-83743 | biostudies-arrayexpress

Pre-transplant conditioning propagates selective loss of host Helios+/Nrp1+ Treg in aHSCT

Project description:Comparative analysis of four murine Treg subsets differentially affected by pre-transplant conditioning and acute gastrointestinal GvHD following allogeneic hematopoietic stem cell transplantation.

2023-03-27 | GSE227929 | GEO

Donor T cells in ovarian graft versus host disease

Project description:Analysis of donor CD4+ and CD8+ T cells purified from spleens and ovaries after murine syngeneic and allogeneic hematopoietic stem cell transplantation Infertility associated with ovarian failure is a serious late complication for female survivors of allogeneic hematopoietic stem cell transplantation (SCT). While the role of pretransplant conditioning regimen has been well appreciated, increasing application of reduced-intensity conditioning facilitated us to revisit the other factors possibly affecting ovarian function after allogeneic SCT. We have addressed whether donor T-cell mediated graft-versus-host disease (GVHD) could be causally related to female infertility in mice. To study transcriptomes of donor T cells infiltrating into the ovary, donor T cells were sorted from recipients' ovaries and microarray analysis was performed.

2017-05-12 | GSE81397 | GEO

Signatures of GVHD and Relapse after Post-Transplant Cyclophosphamide Revealed by Immune Profiling and Machine Learning [17618R]

Project description:Lymphocyte subsets (CD8, CD4 Tconv, CD4 Treg) were sorted from patients' peripheral blood obtained 180 days after matched-donor allogeneic bone marrow transplantation followed by posttransplant cyclophosphamide (PTCy) as a single agent GVHD prophylaxis (NCT00809276). Cohort of patients developed GVHD, or remained GVHD-free. RNA-sequencing was performed to analyze the transcriptional landscape of alloresponse in post-PTCy breakthrough GVHD.

2021-09-28 | GSE182678 | GEO

Signatures of GVHD and Relapse after Post-Transplant Cyclophosphamide Revealed by Immune Profiling and Machine Learning [15065R]

Project description:Lymphocyte subsets (CD8, CD4 Tconv, CD4 Treg) were sorted from patients' peripheral blood obtained on day 28 after matched-donor allogeneic bone marrow transplantation followed by posttransplant cyclophosphamide (PTCy) as a single agent GVHD prophylaxis (NCT00809276). Cohort of patients developed GVHD, or remained GVHD-free. RNA-sequencing was performed to analyze the transcriptional landscape of alloresponse in post-PTCy breakthrough GVHD.

2021-09-28 | GSE182610 | GEO

Molecular plasticity of regulatory T cells in allogeneic stem cell transplantation

Project 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. Student´s t-test was used to identify significant expression changes.

2010-12-31 | E-GEOD-23332 | biostudies-arrayexpress

Faecal Microbiota Transplantation After Allogeneic Stem Cell Transplantation

Project description:The aim of this study is to assess the Fecal Microbiota Transplantation (FMT) efficacy in the prevention of allogeneic hematopoietic stem cell transplantation (allo-HSCT) complications and particularly Graft versus Host Disease (GvHD). The hypothesis of this study is that allogeneic FMT may improve outcomes of these patients.

| 2381286 | ecrin-mdr-crc

Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites (Cohort 2)

Project description:Despite improvement in clinical management, allogeneic hematopoietic stem cell transplantation (HSCT) is still hampered by high morbidity and mortality rates, mainly due to Graft versus host disease (GvHD). Recently, it has been demonstrated that the allogeneic immune response might be influenced by external factors such as tissues microenvironment or host microbiota.Here we used high throughput metabolomics (UPLC-MS/MS) in two cohorts of genotypically HLA-identical related recipient and donor pairs. A first monocentric cohort from Saint Louis hospital (Paris, France) was used as an exploratory cohort (n=43) and a second multicentric national cohort from Cryostem biobank was used as a confimatory cohort (n=56).Metabolomic profile markedly differed between recipients and donors. At the onset of acute GvHD, in addition to host-derived metabolites, we identified significant variation in microbiota-derived metabolites, especially in Aryl hydrocarbon Receptor (AhR) ligands, bile acids and plasmalogens. Altogether, our findings support that the allogeneic immune response during acute GvHD might be influenced by bile acids and by the decreased production of AhR ligands by microbiota that could limit indoleamine 2,3-dioxygenase (IDO) induction and influence allogeneic T-cell reactivity. <a href='https://www.ebi.ac.uk/metabolights/editor/study/MTBLS204/descriptors' rel='noopener noreferrer' target='_blank'>MTBLS204</a> contains study information relating to cohort 1.<a href='https://www.ebi.ac.uk/metabolights/editor/study/MTBLS205/descriptors' rel='noopener noreferrer' target='_blank'>MTBLS205</a> contains study information relating to cohort 2.

2019-11-06 | MTBLS205 | MetaboLights

Metabolomics analysis of human acute graft-versus-host disease reveals changes in host and microbiota-derived metabolites (Cohort 1)

2019-11-06 | MTBLS204 | MetaboLights

Immune Mediated Disorders after Allo-HCG

Project description:Allogeneic hematopoietic cell transplantation (HCT) is the only known curative option for many hematologic disorders. After transplantation, many patients develop immune mediated disorders that may be life-threatening. Post-HCT immune mediated disorders are rare relative to other diseases but the prototype of graft versus host disease (GVHD) develops in 30-70% of patients. The morbidity and mortality associated with these HCT-associated immune mediated disorders are major barriers to successful use of transplantation to cure rare hematologic malignancies such as leukemia, lymphoma, multiple myeloma, myelodysplastic/myeloproliferative syndromes amongst other diseases. The purpose of this study is to characterize and more completely define the onset and course of immune mediated disorders after allogeneic HCT, focusing on participants who develop cutaneous sclerosis, bronchiolitis obliterans syndrome (BOS), late acute graft-vs.-host disease (GVHD), and chronic GVHD. <ul> <li>Of the participants undergoing allogeneic hematopoietic cell transplantation (HCT), can we, the researchers better identify who will develop immune-mediated disorders, what types of disorders participants will have, and whether these disorders will be severe or respond to currently available therapies?</li> </ul> This is a longitudinal study of 1118 individuals (1081 adults and 100 children). Those participating in this study will be evaluated over a 3 year period at 9 study sites. Participants will be enrolled pre-transplant, or up to day 121 post transplantation. This wide enrollment window will allow sites to use recruitment methods that are most efficient at their institutions. At least 2 years of follow-up will ensure an adequate sample size, and sufficient time for observation of the full spectrum of immune mediated disorders. The data of 1023 individuals have been submitted to dbGaP.

| phs001331 | dbGaP

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