Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell profiling of CD4+ T cells from human fetal intestine

ABSTRACT: The fetus is thought to be protected from exposure to foreign antigens, yet CD45RO+ T-cells reside in the fetal intestine. We combined functional assays with mass cytometry, single-cell RNA-sequencing, and high-throughput TCR-sequencing to characterize the fetal intestinal CD4+ T-cell compartment. We identified 22 CD4+ T-cell clusters, including naive-like, regulatory-like, and memory-like subpopulations, which were confirmed and further characterized at the transcriptional level. Memory-like cells expressed high levels of Ki-67, indicating cell division, and CD5, a surrogate marker of TCR-avidity, and produced IFN-γ and IL-2. Pathway analysis revealed a differentiation trajectory associated with cellular activation and proinflammatory effector functions, and TCR-repertoire analysis demonstrated clonal expansions, distinct repertoire characteristics, and interconnections between subpopulations of memory-like CD4+ T-cells. Imaging-mass cytometry further showed that memory-like CD4+ T-cells colocalized with antigen-presenting cells. Collectively, these results provided evidence for the generation of memory-like CD4+ T-cells in the human fetal intestine, consistent with exposure to foreign antigens.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122846 | GEO | 2018/11/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Deciphering and predicting CD4+ T cell immunodominance of Influenza virus hemagglutinin

Project description:The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naïve and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naïve and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naïve CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naïve T cells specific for cryptic H1-HA peptides, and demonstrate that antigen processing represents a major constraint determining immunodominance.

2020-06-29 | PXD018151 | Pride

ChIP-Seq analysis C57BL/6 thymocytes

Project description:In this study, we show that in addition to regulating DP thymocytes survival, RORgT also controls genes that regulate thymocyte migration, proliferation, and T cell receptor (TCR) selection. Strikingly, pharmacological inhibition of RORg skews TCR gene rearrangement, limits T cell repertoire diversity, and inhibits development of autoimmune encephalomyelitis. Thus, targeting RORgT not only inhibits Th17 cell development and function but also fundamentally alters thymic-emigrant recognition of self and foreign antigens.

2016-10-20 | GSE88916 | GEO

Single-cell transcriptional profiling identifies a spectrum of unconventional intraepithelial T lineage cells in human cord blood

Project description:Conventional CD4 and CD8 single positive T cell lineages constitute the main differentiation pathway in the thymus. In human thymus, a minor TCRαβ differentiation pathway diverges from the early double positive stage, consisting of CD10+ PD-1+ cells. These cells are phenotypically and functionally similar to murine agonist-selected intraepithelial T lymphocyte precursors (IELps) which home to the small intestine. Here, the progeny of the human agonist-selected IEL lineage was identified in antigen-inexperienced cord blood (CB) with a polyclonal T cell receptor (TCR) repertoire exhibiting a bias towards early TCR alpha chain rearrangements and elevated autoreactive indices. Single-cell RNA sequencing allowed further delineation of this unconventional lineage in CB. Trajectory analysis, along with TCR repertoire analysis, transcriptomics and proteomics, suggests a precursor-progeny relationship with the thymic IELps. The distinct, heterogeneous CB population can now be defined as CD3+ TCRαβ+ CD4- CCR7- CD26-. Besides recent thymic emigrants, this population also consists of newly identified effector clusters and previously described populations: the suppressive NK receptor expressing CD8+ Treg population, the KIR/NKG2A+ EOMES+ virtual memory population and the CD8αα+ T cell populations. The population shows a discriminating stable HELIOS expression and is exclusively able to downregulate CD8β expression, resulting in double negative T cells. The functional properties of this population suggest that the cells expand on inflammatory cues and exert cytotoxic and proinflammatory activity.

2023-02-10 | PXD033392 | Pride

Single-cell multiomics sequencing (RNA, ADT and VDJ) of CD4+ T cells from peripheral blood of CMV+ and CMV- healthy humans.

Project description:The goal of this study is to understand the transcriptional features of CD4+ memory T cells induced by CMV seropositivity and explore their TCR repertoire clonality.

2021-03-30 | GSE167272 | GEO

Expression data from virus-specific mouse Th1 and Tfh CD4 T cell subsets after LCMV infection

Project description:CD4 T follicular helper (Tfh) cells provide the required signals to B cells for germinal center reactions that are necessary for longlived antibody responses. However, it remains unclear whether there are CD4+ memory T cells committed to the Tfh lineage after antigen clearance. Using adoptive transfer of antigen-specific memory CD4+ subpopulations (based on CXCR5 and Ly6c expression)in the LCMV infection model, we found that there are distinct memory CD4+ T cell populations with commitment to the Tfh and Th1 lineages. Our conclusions are based on gene expression profiles, epigenetic studies and phenotypic and functional analysis. The gene expression profiles of virus-specific CD4 T cell subets at effector and memory stages is presented here. The SMARTA TCR transgenic / adptive transfer system was used to identify and sort subsets of antigen-specific CD4 T cells (based on their expression of Ly6c and CXCR5) elicited after acute infection with LCMV (Arm).

2013-04-22 | E-GEOD-43863 | biostudies-arrayexpress

Anti-CD4 treatment affects TCR repertoire of CD8+ T cells

Project description:Anti-CD4 monoclonal antibody, a prominent immunomodulatory agent, elicits robust anti-tumor immunity in various cancers by increasing tumor-infiltrating lymphocytes and promoting CD8+ T cell reactivity against tumor cell-derived antigens. We conducted TCR repertoire analysis of anti-CD4-exposed endogenous CD8+ T cells to investigate the expansion pattern of the cell population.

2021-08-03 | GSE181280 | GEO

Profiling site specific TCR diversity of CD4+ T Cells in mice undergoing cardiac dysfunction

Project description:Purpose: Despite the well-established association between T cell-mediated inflammation and non-ischemic heart failure (HF), the specific mechanisms triggering T cell activation during the progression of HF and the antigens involved are poorly understood. We hypothesized that clonal expansion of CD4+ T cell in response to cardiac neoantigens promote the progression of HF. Methods: We used transverse aortic constriction (TAC) in mice to trigger HF and profiled the TCR repertoire by mRNA sequencing of CD4+ T cells from 3 pooled Nur77GFP reporter mice, which transiently express GFP upon TCR engagement. We performed TCR clonal analysis of 5000 TCR-activated GFP+CD4+ T cells sorted from the LV, and 5000 CD4+ T cells sorted from the thymus, the inguinal lymph nodes (iLNs) and the heart-draining mediastinal lymph nodes (mLNs) by bulk RNA sequencing of the TCR beta chain after 8wks of TAC surgery. Paired‐end 300 base pair reads were obtained by Illumina sequencing and aligned and assembled using MiXCR software. Results: As expected, the greatest number of unique TCR beta clonotypes (4412 clones) – and therefore the highest TCR diversity – was identified in the thymus. The heart draining mLNs showed a much lower degree of TCR clonal diversity relative to the peripheral iLNs, suggesting that cardiac antigen-driven clonal expansion occurs at the mLNs that directly drain the heart. TCR-activated GFP+CD4+ T cells in the LV represented even lower TCR diversity relative to other sites. Conclusion: Collectively, our study demonstrates that in response to cardiac pressure overload, CD4+ T cells clonally expand in the heart-draining mLN; whilst a limited repertoire of CD4+ T cell clones engage endogenous antigens in the heart.

2020-11-11 | GSE161172 | GEO

T cell reperoire sequencing of donor and patient samples after abT/CD19-depleted allogenic HSCT with CD45RA-depleted DLI

Project description:To track for T cell clones from donor memory T cell fraction infused after abT/CD19-depleted allogenic HSCT we performed TCR beta repertoire sequencing. Patient peripheral blood repertoire was sequenced in two timepoints (p3 and p4: d120-180 and d360-500). Reperotoires for bulk and CD4+ or CD8+ cells from CD45RA-depleted donor apheresis were obtained for most donor-recipient pairs. TCR beta cDNA libraries were prepared using previously published protocol (Zvyagin I.V. et al., Leukemia, 2017). Libraries were sequenced on Illumina NextSeq 500/550 and HiSeq2000/2500 in pair-end mode with read length 100-150 bp. MiGEC software were used for demultiplexing and unique molecular identifier sequence extraction software (https://github.com/mikessh/migec).

2020-07-01 | E-MTAB-8874 | biostudies-arrayexpress

Machine learning analysis of the T cell receptor repertoire identifies sequence features that predict self-reactivity

Project description:The T cell receptor (TCR) determines the specificity and affinity for both foreign and self-peptides presented by MHC. It is established that self-pMHC reactivity impacts T cell function, but it has been challenging to identify TCR sequence features that predict T cell fate. To discern patterns distinguishing TCRs from naïve CD4+ T cells with low versus high self-pMHC reactivity, we used data from 42 mice to train a machine learning (ML) algorithm that predicts self-reactivity directly from TCRβ sequences. This approach revealed that n-nucleotide additions and acidic amino acids weaken selfreactivity. We tested our ML predictions of TCRβ sequence self-reactivity using retrogenic mice. Extrapolating our analyses to independent datasets, we found high predicted self-reactivity for regulatory CD4+ T cells and low predicted self-reactivity for T cells responding to chronic infection. Our analyses suggest a potential trade-off between repertoire diversity and self-reactivity intrinsic to the architecture of a TCR repertoire.

2023-01-09 | GSE221703 | GEO

Altered transcriptional programming in Nur77-GFPhi naïve CD8 T cells

Project description:Naive T cells experience accumulation of TCR signaling in response to self-antigens in the steady state. However, how these signals influence the responsiveness of naive CD8+ T cells to subsequent agonist TCR stimulation remains incompletely understood. We investigated how naive CD8+ T cells that experienced relatively low or high levels of TCR signaling in response to self-antigens respond to stimulation with foreign antigens. A transcriptional reporter of Nr4a1 (Nur77-GFP) revealed substantial heterogeneity of the amount of TCR signaling naive CD8+ T cells accumulate in the steady state. To further understand the impact of differential TCR signaling on CD8 T cells we performed RNA-seq on naive Nur77-GFPhi and lo populations.

2023-03-02 | GSE223457 | GEO

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