Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Circulating ?4?7+ Memory T Cells in Pediatric IBD Patients Express a Polyclonal T Cell Receptor Repertoire

ABSTRACT: Background The integrin ?4?7 is highly expressed on activated T cells and is thought to direct homing of lymphocytes to the intestine. Since ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by mucosal oligoclonal T cells’ expansion, we aimed to assess whether similar repertoire features are identified in circulating gut-specific memory T cells. Methods Memory CD3+ T cells were isolated from blood samples of control subjects and patients with active UC or CD and then FACS-sorted into ?4?7+ and ?4?7? populations. DNA was extracted from each subset and subjected to next-generation sequencing of the TCR?. Different repertoire characteristics were compared between ?4?7+ and ?4?7? subsets for each subject, and between groups. Results The percentages of memory T cells and ?4?7+ cells were comparable between groups. ?4?7+ memory T cells displayed a polyclonal distribution, in control subjects and in UC or CD patients, with similar indices of diversity. Strikingly, the clonal overlap between ?4?7+ and ?4?7? T cells for each subject in all three groups was high, ranging between 20%–50%. We were unable to identify shared T cell clones that were specific to one of the groups. Conclusion ?4?7+ memory T cells exhibited a polyclonal repertoire in both control subjects and patients with active inflammatory bowel disease, with high rates of overlap with ?4?7? memory T cells. Our study, along with additional recent reports, may suggest that the suppression of intestinal inflammation by vedolizumab is independent of the drug’s effect on T cell migration to the gut.

SUBMITTER: Gamliel A

PROVIDER: S-EPMC7537844 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Polyclonal T-cells express CD1a in Langerhans cell histiocytosis (LCH) lesions.

Project description:Langerhans cell histiocytosis (LCH) is a complex and poorly understood disorder that has characteristics of both inflammatory and neoplastic disease. By using eight-colour flow cytometry, we have identified a previously unreported population of CD1a(+)/CD3(+) T-cells in LCH lesions. The expression of CD1a is regarded as a hallmark of this disease; however, it has always been presumed that it was only expressed by pathogenic Langerhans cells (LCs). We have now detected CD1a expression by a range of T-cell subsets within all of the LCH lesions that were examined, establishing that CD1a expression in these lesions is no longer restricted to pathogenic LCs. The presence of CD1a(+) T-cells in all of the LCH lesions that we have studied to date warrants further investigation into their biological function to determine whether these cells are important in the pathogenesis of LCH.

| S-EPMC4208746 | biostudies-literature

Gene expression profiles of pediatric IBD remission patients

Project description:Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients.

2013-10-04 | GSE33943 | GEO

Gene expression profiles of pediatric IBD remission patients

Project description:Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation We performed (un)supervised clustering analysis of IBD-associated genes and applied IngenuityM-BM-. pathway software to identify specific molecular profiles between patients. We analyzed RNA gene expression profiles of peripheral blood leucocytes (PBL) from pediatric IBD patients in clinical remission and age-matched controls.

2013-10-04 | E-GEOD-33943 | biostudies-arrayexpress

Pediatric IBD MLI metaproteomics

Project description:Mucosal-luminal interface (MLI) samples were collected from a cohort of children with new-onset IBD and microbial cells were harvested and processed for metaproteomic analysis. Deep metaproteomics data analysis was then performed for better understanding the MLI microbiota functions in the development of pediatric IBD.

2018-08-03 | PXD007819 | Pride

Bispecific T-cells expressing polyclonal repertoire of endogenous ?? T-cell receptors and introduced CD19-specific chimeric antigen receptor.

Project description:Even though other ?? T-cell subsets exhibit antitumor activity, adoptive transfer of ?? Tcells is currently limited to one subset (expressing V?9V?2 T-cell receptor (TCR)) due to dependence on aminobisphosphonates as the only clinically appealing reagent for propagating ?? T cells. Therefore, we developed an approach to propagate polyclonal ?? T cells and rendered them bispecific through expression of a CD19-specific chimeric antigen receptor (CAR). Peripheral blood mononuclear cells (PBMC) were electroporated with Sleeping Beauty (SB) transposon and transposase to enforce expression of CAR in multiple ?? T-cell subsets. CAR(+)?? T cells were expanded on CD19(+) artificial antigen-presenting cells (aAPC), which resulted in >10(9) CAR(+)?? T cells from <10(6) total cells. Digital multiplex assay detected TCR mRNA coding for V?1, V?2, and V?3 with V?2, V?7, V?8, V?9, and V?10 alleles. Polyclonal CAR(+)?? T cells were functional when TCR?? and CAR were stimulated and displayed enhanced killing of CD19(+) tumor cell lines compared with CAR(neg)?? T cells. CD19(+) leukemia xenografts in mice were reduced with CAR(+)?? T cells compared with control mice. Since CAR, SB, and aAPC have been adapted for human application, clinical trials can now focus on the therapeutic potential of polyclonal ?? T cells.

| S-EPMC3589159 | biostudies-literature

Gammaherpesvirus-infected germinal center cells express a distinct immunoglobulin repertoire.

Project description:The gammaherpesviruses (γHVs), human Kaposi sarcoma-associated herpesvirus (KSHV), EBV, and murine γHV68 are prevalent infections associated with lymphocyte pathologies. After primary infection, EBV and γHV68 undergo latent expansion in germinal center (GC) B cells and persists in memory cells. The GC reaction evolves and selects antigen-specific B cells for memory development but whether γHV passively transients or manipulates this process in vivo is unknown. Using the γHV68 infection model, we analyzed the Ig repertoire of infected and uninfected GC cells from individual mice. We found that infected cells displayed the hallmarks of affinity maturation, hypermutation, and isotype switching but underwent clonal expansion. Strikingly, infected cells displayed distinct repertoire, not found in uninfected cells, with recurrent utilization of certain Ig heavy V segments including Ighv10-1 In a manner observed with KSHV, γHV68 infected cells also displayed lambda light chain bias. Thus, γHV68 subverts GC selection to expand in a specific B cell subset during the process that develops long-lived immunologic memory.

| S-EPMC7012147 | biostudies-literature

Molecular Genetic Architecture of Monogenic Pediatric IBD Differs from Complex Pediatric and Adult IBD.

Project description:Inflammatory bowel disease (IBD) manifests as a complex disease resulting from gene-environment interactions or as a monogenic disease resulting from deleterious mutations. While monogenic IBD is predominantly pediatric, only one-quarter of complex IBD is pediatric. In this study, we were the first to systematically compare genetic architecture between monogenic and complex pediatric and adult IBD on genetic and molecular pathway levels. Genes reported as causal for monogenic pediatric IBD and related syndromes and as risk factors for pediatric and adult complex IBD were analyzed using CytoScape and ClueGO software tools to elucidate significantly enriched Gene Ontology (GO) terms. Despite the small overlap (seven genes) between monogenic IBD genes (85) and complex IBD loci (240), GO analysis revealed several enriched GO terms shared between subgroups (13.9%). Terms Th17 cell differentiation and Jak/STAT signaling were enriched in both monogenic and complex IBD subgroups. However, primary immunodeficiency and B-cell receptor signaling pathway were specifically enriched only for pediatric subgroups, confirming existing clinical observations and experimental evidence of primary immunodeficiency in pediatric IBD patients. In addition, comparative analysis identified patients below 6 years of age to significantly differ from complex pediatric and adult IBD and could be considered a separate entity.

| S-EPMC7712254 | biostudies-literature

Characteristics of T-cell receptor repertoire of stem cell-like memory CD4+ T cells.

Project description:Stem cell-like memory T cells (Tscm) combine phenotypes of naïve and memory. However, it remains unclear how T cell receptor (TCR) characteristics contribute to heterogeneity in Tscm and other memory T cells. We compared the TCR-beta (TRB) repertoire characteristics of CD4+ Tscm with those of naïve and other CD4+ memory (Tm) in 16 human subjects. Compared with Tm, Tscm had an increased diversity across all stretches of TRB repertoire structure, a skewed gene usage, and a shorter length distribution of CDR3 region. These distinctions between Tscm and Tm were enlarged in top1000 abundant clonotypes. Furthermore, top1000 clonotypes in Tscm were more public than those in Tm and grouped in more clusters, implying more epitope types recognized by top1000 clonotypes in Tscm. Importantly, self-reactive clonotypes were public and enriched in Tscm rather than Tm, of type one diabetes patients. Therefore, this study highlights the unique features of Tscm different from those of other memory subsets and provides clues to understand the physiological and pathological functions of Tscm.

| S-EPMC8401816 | biostudies-literature

Deep Sequencing of the T-cell Receptor Repertoire Demonstrates Polyclonal T-cell Infiltrates in Psoriasis.

Project description:It is well known that infiltration of pathogenic T-cells plays an important role in psoriasis pathogenesis. However, the antigen specificity of these activated T-cells is relatively unknown. Previous studies using T-cell receptor polymerase chain reaction technology (TCR-PCR) have suggested there are expanded T-cell receptor (TCR) clones in psoriatic skin, suggesting a response to an unknown psoriatic antigen. Here we describe the results of high-throughput deep sequencing of the entire ??- and ??- TCR repertoire in normal healthy skin and psoriatic lesional and non-lesional skin. From this study, we were able to determine that there is a significant increase in the abundance of unique ?- and ?- TCR sequences in psoriatic lesional skin compared to non-lesional and normal skin, and that the entire T-cell repertoire in psoriasis is polyclonal, with similar diversity to normal and non-lesional skin. Comparison of the ??- and ??- TCR repertoire in paired non-lesional and lesional samples showed many common clones within a patient, and these close were often equally abundant in non-lesional and lesional skin, again suggesting a diverse T-cell repertoire. Although there were similar (and low) amounts of shared ?-chain sequences between different patient samples, there was significantly increased sequence sharing of the ?-chain in psoriatic skin from different individuals compared to those without psoriasis. This suggests that although the T-cell response in psoriasis is highly polyclonal, particular ??- T-cell subsets may be associated with this disease. Overall, our findings present the feasibility of this technology to determine the entire ??- and ??- T-cell repertoire in skin, and that psoriasis contains polyclonal and diverse ??- and ??- T-cell populations.

| S-EPMC4648215 | biostudies-literature

Seroconversion Following SARS-CoV-2 Infection or Vaccination in Pediatric IBD Patients.

Project description: Not available

| S-EPMC8499751 | biostudies-literature