Gene expression data from CD8+ T cell subsets
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE241027 | GEO | 2024/01/24
REPOSITORIES: GEO
Similar Datasets
Project description:As humans age their memory T cell compartment expands due to lifelong exposure to antigens. This expansion is characterized by the presence of terminally differentiated CD8+ T cells (Temra) which possess an NK cell-like phenotype and are associated with chronic inflammatory conditions. Temra cells are predominantly driven by sporadic cytomegalovirus reactivation (CMV) yet their cellular heterogeneity remains understudied. To address this gap we measured their gene expression profiles and conducted single-cell transcriptome analysis. We show that CD8+ Temra cells are highly heterogeneous and describe subsets specific to old age and CMV infection.
2024-01-23 | GSE241493 | GEO
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. C57BL/6 mice were infected intraperitoneally (i.p.) with MCMV strain MW97.01 between 6-16 weeks of age. Splenocytes were isolated from chronically-infected mice and co-stained with three PE-conjugated tetramers loaded with the antigenic peptides from M38, m139 and IE3, all of which promote memory inflation. Cells were then stained with fluorescently conjugated antibodies and sorted on a MoFlo cell sorter. Naïve CD8+ cells were identified as CD44lo. MCMV-specific T cells were identified as CD8+, CD44hi and tetramer binding and then further segregated into memory and effector cells subsets by their expression of KLRG1 and CD127.
2015-01-28 | E-GEOD-61927 | biostudies-arrayexpress
Project description:The CD8+ T cell compartment of human cytomegalovirus (CMV) seropositive individuals characteristically contains a high proportion of cells that expresses Natural Killer Cell Receptors (NKR) which may contribute to the surveillance of virus-infected cells. To test if this enhanced expression is a direct and immediate result of CMV infection we used DNA microarrays to analyse putative changes in RNA-expression level of 39 NKRs in CMV-specific CD8+ T cells of renal transplant recipients experiencing primary CMV infection. Already in the acute phase of infection 29 NKRs were induced of which 19 remained high 1 year after cessation of viral replication. Activating and inhibitory NKRs were induced to a similar extent. Detailed longitudinal flowcytometric analyses confirmed NKR changes at the protein level. Strikingly, a strong induction of CD94 on CD3+ T cells was observed with surface expression of activating CD94dimNKG2C dimers appearing before inhibitory CD94brightNKG2A ones. After the acute phase of infection, the balance between inhibitory and activating receptors did not change. Thus, CMV infection induces a rapid and lasting change in the expression of NK receptors on human CD8+ T cells. Keywords: primary cytomegalovirus infection, human, CD8+ T cells, NKR, latent infection, chronic infection CMV-specific CD8+ T cells were isolated at three different stages (peak, 1 year p.i, latent) from three CMV seropositive individuals. Total RNA for each stage was pooled and compared with pooled RNA of naive CD8+ T-cells from healthy controls. For quality control naive CD8+ T-cells were compared with naive CD8+ T-cells. The experiment was performed in dye-swap.
2008-08-28 | E-GEOD-12589 | biostudies-arrayexpress
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.
2015-01-28 | GSE61927 | GEO
Project description:Human CD8+ T cells are functionally heterogeneous and can be divided into distinct subsets according to CCR7 and CD45RA expression levels. Among the subsets, CCR7-CD45RA+ CD8+ T cells are considered to be terminally differentiated cells and designated as Temra. Temra show attenuated ability to proliferate and produce IFN-gamma in response to TCR stimulation, while Temra show improved function after IL-15 treatment. To clarify the transcriptional signatures induced by the stimulations, Temra were purified using flow cytometry, stimulated with IL-15 or with anti-CD3/CD28 (TCR stimulation), or cultured without stimulation for 2 days, and subjected to microarray analysis.
2015-12-01 | GSE69072 | GEO
Project description:The CD8+ T cell compartment of human cytomegalovirus (CMV) seropositive individuals characteristically contains a high proportion of cells that expresses Natural Killer Cell Receptors (NKR) which may contribute to the surveillance of virus-infected cells. To test if this enhanced expression is a direct and immediate result of CMV infection we used DNA microarrays to analyse putative changes in RNA-expression level of 39 NKRs in CMV-specific CD8+ T cells of renal transplant recipients experiencing primary CMV infection. Already in the acute phase of infection 29 NKRs were induced of which 19 remained high 1 year after cessation of viral replication. Activating and inhibitory NKRs were induced to a similar extent. Detailed longitudinal flowcytometric analyses confirmed NKR changes at the protein level. Strikingly, a strong induction of CD94 on CD3+ T cells was observed with surface expression of activating CD94dimNKG2C dimers appearing before inhibitory CD94brightNKG2A ones. After the acute phase of infection, the balance between inhibitory and activating receptors did not change. Thus, CMV infection induces a rapid and lasting change in the expression of NK receptors on human CD8+ T cells. Keywords: primary cytomegalovirus infection, human, CD8+ T cells, NKR, latent infection, chronic infection
2008-08-28 | GSE12589 | GEO
Project description:Neuroinflammation in the brain contributes to the pathogenesis of Parkinson’s disease (PD), but the potential dysregulation of peripheral immunity has not been systematically investigated for idiopathic PD (iPD). Here we showed an elevated peripheral cytotoxic immune milieu, with more terminally-differentiated effector memory (TEMRA) CD8 T, CD8+ NKT cells and circulating cytotoxic molecules in fresh blood of early-to-mid iPD, especially in females, after analyzing >700 innate and adaptive features. This profile, also reflected by fewer CD8+FOXP3+ regulatory T cells, was confirmed in another subcohort. Co-expression between cytotoxic molecules was selectively enhanced in CD8 TEMRA and effector memory (TEM) cells. Single-cell RNA-sequencing analysis demonstrated the accelerated CD8 differentiation within CD8 compartments, enhanced cytotoxic pathways in CD8 TEMRA and TEM cells, while CD8 central-memory (TCM) and naïve cells were already more-active and transcriptionally-reprogrammed. Our work provides a comprehensive map of dysregulated peripheral immunity in iPD, proposing previously-unrecognized candidates for early diagnosis and treatments.
2023-10-13 | GSE237254 | GEO
Project description:Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses. Total RNA was extracted from sorted memory CD8 T cells induce by CMV and adenoviral vectors, and naïve CD8 cells
2015-09-23 | E-GEOD-73314 | biostudies-arrayexpress
Project description:Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naïve (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of TN and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.
2005-01-01 | E-TABM-40 | biostudies-arrayexpress
Project description:To obtain the differentiated profiling of long noncoding RNA expression between CD8+CD28+ T cell subset and CD8+CD28- T cell subset, we have detecte lncRNA profiling between within-individual T cell subsets to identify differentiated lncRNA profiling in five apperant healthy Chinese nenogenarians who were cytomegalovirus-seropositive carriers. Human peripheral blood monocytes from these apperantly healthy CMV-seropositive nonagenarians was gathered. CD8+CD28+ T cells and CD8+CD28- T cells were further isolated using flow cytometry. Differentiated lncRNA profiling was compared between CD8+CD28+ T cells and CD8+CD28- T cells using lncRNA microarry detection within-individually. 586 lncRNAs were found significantly upregulated while 1113 lncRNAs were found significantly downregulated comparing CD8+CD28+ T cells with CD8+CD28- T cells in these Chinese nonagenarians with CMV seropositivity. Expression of ENST00000446590,NR_121652,NR_045006,ENST00000428936,NR_110375 from this differentiated profiling which were identified as previously domumented ageing-related lncRNAs were quantified in the same RNA samples by real-time PCR, confirming lncRNAs take critical role in regulating T cell immunosenesence in healthy nonagenarian Chinese CMV carriers. Diffentiated lncRNA profiling was in-pair compared between total RNAs isolated from CD8+CD28+ T cells and CD8+CD28- T cells within-individually in Chinese nonagenarian CMV carriers.
2016-10-15 | GSE88767 | GEO