CMV-CTLs scVDJ-RNAseq
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA659230 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12514541_1.fastq.gz | Fastqsanger.gz | |||
| SRR12514541_2.fastq.gz | Fastqsanger.gz | |||
| SRR12514542_1.fastq.gz | Fastqsanger.gz | |||
| SRR12514542_2.fastq.gz | Fastqsanger.gz | |||
| SRR12514543_1.fastq.gz | Fastqsanger.gz |
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Project description:We conducted immune- and RNA-sequencing of HLA-A24-restricted CMVpp65-specific CTLs to better understand the immune reconstitution of CMV-CTLs after allo-HCT. To the best of our knowledge, this is the first report on the features of TCRβ-CDR3, diversity, and GEP of HLA-A24 CMV-CTLs according to the CMV-reactivation pattern among recipients after allo-HCT. In addition, we further sought to demonstrate homogeneity or heterogeneity according to individual CTL clones using single-cell RNA-sequencing technology.
2021-01-01 | GSE156841 | GEO
Project description:We conducted immune- and RNA-sequencing of HLA-A24-restricted CMVpp65-specific CTLs to better understand the immune reconstitution of CMV-CTLs after allo-HCT. To the best of our knowledge, this is the first report on the features of TCRβ-CDR3, diversity, and GEP of HLA-A24 CMV-CTLs according to the CMV-reactivation pattern among recipients after allo-HCT. In addition, we further sought to demonstrate homogeneity or heterogeneity according to individual CTL clones using single-cell RNA-sequencing technology.
2021-06-28 | GSE179009 | GEO
Project description:CMV-specific cytotoxic T lymphocytes (CTLs) RNA-seq at the early phase of allo-HCT
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Project description:CMV-specific cytotoxic T lymphocytes (CTLs) RNA-seq at the late phase of allo-HCT
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Project description:Interventions: Patients with the detection of either cytomegalic cells or IHC-CMV cells were diagnosed with CMV colitis.,Patients older than 18 years with clinical suspicion of CMV colitis but negative biopsy for CMV.,Asymptomatic patients underwent colonoscopy for screening.;Diagnostic,Diagnostic,Diagnostic;CMV colitis,Non-CMV colitis ,Healthy volunteers
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Project description:Reconstitution of cytomegalovirus (CMV)-specific immunity following transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Due to the persistence of CMV, most CMV-specific CD8+ T cells become terminally differentiated effector cells (TEFF). However, a minor subset retains a memory phenotype (TM). Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes may have different abilities to reconstitute sustained immunity following transfer. The immunology of human CMV (HCMV) infections is reflected in the mouse model of MCMV infection. We found that HCMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. After transfer, the proliferative capacity of MCMV-specific TM cells was vastly superior to TEFF cells. Strikingly, TM cells expanded and established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM cells could protect Rag-/- mice, only TM cells could consistently survive after transfer into immune replete, latently infected recipients and respond if recipient immunity was lost. These data show that CMV-specific TM cells retain memory function during persistent infection and can re-establish CMV immunity when necessary.
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Project description:PI3K/Akt pathway plays a central role in T-cell activation and is impaired in Ag-specific CTLs during chronic viral infections. In this study, we genetically engineered HBV-specific CTLs and adoptively transferred these Akt-expressing viral Ag-specific CTLs into HBV-infected mice and monitored the virological and immunological responses. In the meantime, we also analyzed the mRNA profiles of control-CTLs and CTLs-overexpressing Akt1 and Akt2, respectively before adoptive transfer and after in vitro restimulation. We expect to elucidate the potential mechanisms about how the Akt signaling in CTLs prevents T-cell exhaustion and enhance T-cell expansion in the liver during persistent HBV infection from this mRNA-seq analysis.
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Project description:This study was performed in order to determine the gene expression changes associated with CMV infection of glioblastoma cells. CMV has been associated with gliobalstoma but its effects are not well characterized.
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Project description:Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon g–producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases. Keywords: NKG2C; LAK; CTL; NK receptor; IEL; Mucosal Immunity; Celiac Disease
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Project description:The CD4+ T cells expressing cytolytic molecules such as granzymes and perforins have been detected in many diseases and are shown to be enriched in the effector memory expressing CD45RA (TEMRA) in humans, but their origin remains elusive. However, their gene expression profile in comparison to classically defined cytotoxic T lymphocytes (CTLs), the CD8-CTLs has not been well demonstrated, hence their relevance remains debatable. Thus in this study by parallelly analysing the CD4-CTLs and CD8-CTLs, we demonstrate that they are indistinguishable for the cytolytic program with both showing similar gene expression profile and T cell antigen-receptor (TCR) clonal expansion. Further using an integrative multi-omics approach combining the transcriptome, TCR repertoire, and open chromatin profile of CD4+ naïve (CD4-TN) and memory subsets, we discovered a stem-cell memory subset that is pre-committed to CTL program within the CD4+ T cell lineage. Through an in vitro differentiation model we developed CD4+ T cells with cytolytic potential from CD4-TN cells. The in vitro differentiated cells followed the trajectory of different developmental memory subsets from ex vivo CD4+ T cells for transcriptomic patterns as well as open-chromatin landscape. Thus, through this model, we deciphered the molecular signatures of early commitment of CD4-TN cells to cytotoxicity program. Of particular interest was the expression of both longevity as well as cytotoxicity associated gene sets by the in vitro differentiated CD4-CTLs, hence generating long-lived CD4-CTL effectors. This specific property can be further explored for vaccine development as well as testing the efficacy and cell based therapies for precision medicine.
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