RNA-seq analysis of human antigen-specific type 1 regulatory T cells (Tr1)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE160194 | GEO | 2021/10/27
REPOSITORIES: GEO
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Project description:Type 1 regulatory T (Tr1) cells are one of the regulatory T cell subsets that are characterized by the production of high amount of IL-10 and lack of FOXP3 expression. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue molecule and we have previously reported that LAG3 is expressed on IL-10 producing regulatory T cells. However, naturally occurring Tr1 cells in human secondary lymphoid tissue have not been detected. We identified CD4+CD25-LAG3+ T cells in human tonsil. We compared mRNA expression of five CD4+ T cell subsets in tonsil using microarray analysis (CD4+CD25-LAG3+ T cells, CD4+CD25-CXCR5+PD-1+ follicular helper T cells (TFH), CD4+CD25+ T cells, CD4+CD25-LAG3-CD45RO+ cells and CD4+CD25-LAG3-CD45RO- cells). A human tonsil was obtained from a patient undergoing routine tonsillectomy, and five tonsillar CD4+ T cell subsets were sorted (each 1 x 10^5 cells). There is no biological replication.
2016-04-01 | E-GEOD-73927 | biostudies-arrayexpress
Project description:Type 1 regulatory T (Tr1) cells are one of the regulatory T cell subsets that are characterized by the production of high amount of IL-10 and lack of FOXP3 expression. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue molecule and we have previously reported that LAG3 is expressed on IL-10 producing regulatory T cells. However, naturally occurring Tr1 cells in human secondary lymphoid tissue have not been detected. We identified CD4+CD25-LAG3+ T cells in human tonsil. We compared mRNA expression of five CD4+ T cell subsets in tonsil using microarray analysis (CD4+CD25-LAG3+ T cells, CD4+CD25-CXCR5+PD-1+ follicular helper T cells (TFH), CD4+CD25+ T cells, CD4+CD25-LAG3-CD45RO+ cells and CD4+CD25-LAG3-CD45RO- cells).
2016-04-01 | GSE73927 | GEO
Project description:Purpose: To identify gene expression patterns in ex vivo isolated human Tr1 cells. Method: RNA sequencing of total mRNA. Results: Differential gene expression of Tr1 and non-Tr1 CD4+ T memory cells. Conclusions: ex vivo type 1 regulatory T cells have a distinct gene expression profile compared to non-Tr1 CD4+ T cell memory cells.
2021-07-02 | GSE169761 | GEO
Project description:10X technology single-cell RNA-seq was used on tetramer-sorted CD4+ T cells from nanoparticle-treated control mice (NOD.CD4-Cre+ and NOD.Prdm1 flox/flox) and NOD.Prdm1 flox/floxCD4-Cre+ mice to study the role of Prmd1 on the differentiation of TFH cells into TR1 cells. Study evidencies the devolopment linkage between tetramer positive TFH and TR1 based on gene expression gradient. Remarkably, mice lacking Prmd1 fail to develop TR1 cells and their differentation is blocked.
2023-03-27 | GSE182636 | GEO
Project description:Gene expression profiling of in vitro differentiated murine Th cell subsets. Flow cytometrically sorted naive Th cells (CD4+ CD44- Foxp3-) were polyclonally stimulated in vitro for 3 days using 4 µg/ml plate-bound antibody to CD3 (145-2C11) and 2 µg/ml soluble antibody to CD28 (PV-1). Th0 cells were cultured in the absence of exogenous cytokines. Th17 cells were differentiated with 50 ng/ml IL-6 plus 0.5 ng/ml TGF-β. Tr-1 cells were differentiated with 100 ng/ml IL-27 plus 0.5 ng/ml TGF-β. Five biological replicates per Th subset (Th0, Th17, Tr1)
2014-03-20 | E-GEOD-56021 | biostudies-arrayexpress
Project description:We report the bulk-cell-based TCR sequences profiling from high-throughput sequencing of human healthy T-allo10 cells. The T-allo10 cell product is consistently enriched for Tr1 cells, is specifically anergic, and suppresses alloantigen-responsive Teff cells. Analysis of Tr1 cells from the T-allo10 product showed that the both TCRa and TCRb repertoires are highly skewed towards dominant clones and has diverged from the parental CD4+ T cells used to generate the T-allo10 product, non-Tr1 cells from the same T-allo10 product, and Teff cells from the control T-allo product. The data indicate that T-allo10-derived Tr1 cells, but not non-Tr1 cells, undergo clonal expansion in response to the alloantigen stimulation, suggesting that the Tr1 cells are the antigen specific component of the T-allo10 cell product. T-allo10 cells are currently undergoing clinical evaluation for safety in a phase I clinical trial (ClinicalTrials.gov ID: NCT03198234).
2021-10-27 | GSE160274 | GEO
Project description:CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases.
2013-12-20 | GSE53514 | GEO
Project description:CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymphocyte activation gene 3 (LAG-3) as being stably and selectively coexpressed on mouse and human Tr1 cells. We showed the specificity of these markers in mouse models of intestinal inflammation and helminth infection and in the peripheral blood of healthy volunteers. The coexpression of CD49b and LAG-3 enables the isolation of highly suppressive human Tr1 cells from in vitro anergized cultures and allows the tracking of Tr1 cells in the peripheral blood of subjects who developed tolerance after allogeneic hematopoietic stem cell transplantation. The use of these markers makes it feasible to track Tr1 cells in vivo and purify Tr1 cells for cell therapy to induce or restore tolerance in subjects with immune-mediated diseases. The transcriptome of human Tr1 cell clones to that of TH0 cell clones either unstimulated or stimulated for 6 and 16 h. Tr1 and TH0 cell clones were isolated from peripheral blood of 2 Healthy Donors (HDs). mRNA from T cell clones unstimulated (t0, n=4 Tr1 cell clones and n=10 TH0 cell clones) or stimulated with immobilized anti-CD3 and soluble anti-CD28 mAbs (6h and 16h, n=4 Tr1 cell clones and n=5 TH0 cell clones) was isolated. Differential expression of 28869 genes was investigated by whole transcript Affymetric chips.
2013-12-20 | E-GEOD-53514 | biostudies-arrayexpress
Project description:Dendritic cells (DC) play a critical role in the maintenance of tissue homeostasis and in promoting tolerance, thus acting as regulatory cells. Tolerogenic DC (tolDC) represent the cells of choice to fulfill the goal of restoring antigen (Ag)-specific tolerance since they can dampen Ag-specific T cell responses, induce pathogenic T cell exhaustion, and Ag-specific regulatory T cells. Here we efficiently generate tolDC by genetic engineering of monocytes with bidirectional lentiviral vectors co-encoding for immunodominant Ag-derived peptides (Ovalbumin or Matrix Protein 1, Insulin and Gliadin) in combination with IL-10 (DCIL-10/Ag). DCIL-10/Ag secrete high amounts of IL_x0002_10 in the absence of pro-inflammatory cytokines and efficiently modulate Ag-specific CD4+ and CD8+ T cell activation and proliferation in vitro in healthy subjects and Celiac Disease patients. DCIL-10/Ag promote Ag-specific CD49b+LAG-3 + T cells, which display the type 1 T regulatory (Tr1) cell gene signature in vitro. In vivo administration of DCIL-10/Ag promote Ag-specific Tr1 cells and prevent type 1 diabetes development in two murine models of disease. In conclusion, we generate an innovative approach based on the use of autologous engineered DC, which effectively modulate pathogenic CD4+ and CD8+ T cell responses in vitro and in vivo by promoting Ag_x0002_specific Tr1 cells suitable for cell-based therapy for restoring tolerance in T cell mediated diseases
2023-05-02 | GSE199425 | GEO
Project description:Interleukin-10 (IL-10) is essential to maintain intestinal homeostasis. CD4+ T regulatory type 1 (TR1) cells produce large amounts of this cytokine and being therefore currently examined in clinical trials as T-cell therapy in patients with inflammatory bowel disease (IBD). However, factors and molecular signals sustaining TR1 cell regulatory activity still need to be identified in order to optimize the efficiency and to ensure the safety of these trials. We investigated the role of IL-10 signaling in mature TR1 cells in vivo. Double IL-10eGFP Foxp3mRFP reporter mice and transgenic mice with impairment in IL-10 receptor signaling were used to test the activity of TR1 cells in a murine IBD model, a model that resembles the trials performed in humans. The molecular signaling was elucidated in vitro. Finally, we used human TR1 cells, currently employed for cell therapy, to confirm our results. We found that murine TR1 cells expressed functional IL-10 receptor α. TR1 cells with impaired IL-10 receptor signaling lost their regulatory activity in vivo. TR1 cells required IL-10 receptor signaling in order to activate p38 MAP kinase, thereby sustaining IL-10 production, which ultimately mediated their suppressive activity. Finally, we confirmed these data using human TR1 cells. In conclusion TR1 cell regulatory activity is dependent on IL-10 receptor signaling. These data suggest that in order to optimize TR1 cell-based therapy, IL-10 receptor expression has to be taken into consideration.
2016-12-30 | GSE89080 | GEO