Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA148731 | ENA |
REPOSITORIES: ENA
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Project description:The present study reports an unbiased analysis of the genetic profile and regulation of NKG2D expressing CD4 T-cells.An Affymetrix microarray analysis was used to explore the genetic profile of NKG2D+ versus NKG2D- CD4 T-cells. The genetic profile was studied by single gene analysis and gene set enrichment analysis. I found that several immune regulatory receptors was regulated differently in NKG2D+ versus NKG2D- CD4 T-cells. Futhermore, I found that NKG2D+ CD4 T-cells display a genetic profile of cytotoxic T-cells. The gene set enrichment analysis revealed a change in 19 processes, including ARF GTPase activator activity; RNA splicing; Signal transduction; Interspecies interaction between organisms; Regulation of ARF GTPase activity; Cell motility; Mitosis; Cell cycle; Anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process; Induction of apoptosis by extracellular signals; Negative regulation of apoptosis; mRNA export from nucleus; Positive regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle; Cell division; Protein polymerization; Spliceosome assembly; Microtubule-based movement; Immune response; mRNA processing. Human CD4 T-cells were isolated from buffy coat by anti-CD4 conjugated magnetic beads. Memory CD4 T-cells were sorted, labeled with CFSE and stimulated with autologous monocytes pulsed with HCMV. HCMV stimulated CD4 T-cells were sorted as CFSE-NKG2D+ or CFSE-NKG2D- and processed for microarray analysis.
2012-08-14 | E-GEOD-33670 | biostudies-arrayexpress
Project description:Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal TCRalphabeta+/CD4+/NKa+/CD8-/+dim T-large granular lymphocyte (LGL) lymphocytosis. Since healthy individuals show (oligo)clonal expansions of hCMV-specific TCRVbeta+/CD4+/cytotoxic/memory T-cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+ T-LGL. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile (GEP) analysis. Experiment Overall Design: Total RNA was isolated from magnetic-activated cell sorter (MACS)-freshly purified hCMV-stimulated CD69+, hCMV-stimulated CD69- and unstimulated monoclonal CD4+ T-LGL lymphocytes from PB samples from four TCRVbeta+/CD4+ T-LGL lymphocytosis patients (purity of �98%). Briefly, 100 ng of total RNA from each of the 12 purified cell fractions was amplified and labeled using the GeneChip two cycle cDNA synthesis kit and the GeneChip IVT labeling kit (Affymetrix Inc., Santa Clara, CA), respectively. Then it was hybridized to the Human Genome U133 Plus 2.0 Array (Affymetrix). Experiment Overall Design: In parallel, total RNA was also isolated from highly purified (� 98% purity) hCMV-stimulated (specific) CD69+ CD4+ T-lymphocytes isolated from PB samples from hCMV-seropositive healthy donors (n=5, mean age of 36 years) using a FACSAria flow cytometer (BDB). To get pure and highly concentrated RNA, the silica membrane technology NucleoSpin® RNA XS (Macherey-Nagel, Düren, Germany) was used. Total RNA was then amplified, labeled and hybridized to the Human Genome U133 Plus 2.0 Array (Affymetrix) as described above.
2008-10-25 | E-GEOD-12488 | biostudies-arrayexpress
Project description:Expression Data From HCMV-Infected Human Monocytes
| PRJNA103449 | ENA
Project description:Expression Data From HCMV-Infected Human Monocytes Study 2
| PRJNA106539 | ENA
Project description:Expression Data From HCMV-Infected Human Monocytes: Role of EGFR
| PRJNA119959 | ENA
Project description:The latent human Cytomegalovirus (hCMV) infection can pose a serious threat of reactivation and disease occurrence in immune-compromised individuals, as well as burdens the immune system in immune-competent individuals. Though, T cells are at the core of the protective immune response to hCMV infection, a detailed characterization of different T cell subsets involved in protection against the hCMV infection is lacking. Here we analyzed the single-cell transcriptomes and the single-cell T cell antigen receptor (TCR) repertoires of over 8000 hCMV-reactive peripheral T cells isolated from different memory compartments. The hCMV-reactive T cells were highly heterogeneous and consisted of different developmental memory and functional T cell subsets such as, the long-term memory precursors and effectors, T helper-17, T regulatory cells (TREGs) and cytotoxic T lymphocytes (CTLs). The hCMV-antigen specific TREGs were enriched for molecules linked to their suppressive function and interferon response genes. The CTLs were of two types, the pre-effector and effector like. Of particular interest was the mixture of both CD4-CTLs and CD8-CTLs in both the pre-effector and effector cytotoxic clusters, suggesting that both CD4-CTLs and CD8-CTLs share transcriptomic signatures. The huge TCR clonal expansion of both the cytotoxic clusters imply their predominant role in protective immune response to CMV. Further the clonotype sharing between the CTL clusters and the long-term memory clusters, indicate potential progenitors of CD4-CTLs. Together our study has identified many subsets of hCMV-specific memory T cells that may have implication in better understanding the hCMV-specific T cell immunity to design vaccination strategies and therapeutics.
2024-03-20 | GSE235604 | GEO
Project description:We have established that human cytomegalovirus (HCMV) infection modulates the biology of target primary blood monocytes, allowing HCMV to use monocytes as 'vehicles' for its systemic spread. HCMV infection of monocytes results in rapid induction of PI(3)K and NF-kB activity. Integrins, which are upstream of the PI(3)K and NF-kB pathways, were shown to be involved in HCMV binding to and entry into fibroblasts, suggesting that receptor-ligand-mediated signaling following viral binding to integrins on monocytes could trigger the functional changes seen in infected monocytes. We now show that integrin engagement and the activation of the integrin/Src-signaling pathway is essential for the induction of HCMV-infected monocyte motility. To investigate how integrin engagement by HCMV triggers monocyte motility, we examined the infected monocyte transcriptome and found that the integrin/Src-signaling pathway regulates the expression of paxillin, which is an important signal transducer in the regulation of actin rearrangement during cell adhesion and movement. Functionally, we observed that paxillin is activated via the integrin/Src-signaling pathway and is required for monocyte motility. Because motility is intimately connected to cellular cytoskeletal organization, a process that is also important in viral entry, we investigated the role paxillin regulation plays in the process of viral entry of monocytes. New results confirmed that HCMV`s ability to enter target monocytes is significantly inhibited in cells deficient in paxillin expression or that had their integrin/Src/paxillin signaling pathway blocked. From our data, HCMV-cell interactions emerge as an essential trigger for the cellular changes that allow for HCMV entry and hematogenous dissemination. Monocytes were mock-infected, HCMV-infected, or pretreated with PP2 inhibitor prior to HCMV infection. There were three samples analyzed per individual replicate. Three replicates are included. comparative studies with a use of the specific Src kinase activity inhibitor
2010-10-31 | E-GEOD-24238 | biostudies-arrayexpress
Project description:Inflammasomes are multi-protein complexes that control the production of pro-inflammatory cytokines such as IL-1beta. Inflammasomes play an important role in the control of immunity to tumors and infections, and also in autoimmune diseases, but the mechanisms controlling the activation of human inflammasomes are largely unknown. We found that human activated CD4+CD45RO+ memory T-cells specifically suppress P2X7R-mediated NLRP3 inflammasome activation, without affecting P2X7R-independent NLRP3 or NLRP1 inflammasome activation. The concomitant increase in pro-IL-1β production induced by activated memory T-cells concealed this effect. Priming with IFNβ decreased pro-IL-1β production in addition to NLRP3 inflammasome inhibition and thus unmasked the inhibitory effect on NLRP3 inflammasome activation. IFNβ did not suppress NLRP3 inflammasome activation by acting directly on monocytes. The inhibition of pro-IL-1β production and suppression of NLRP3 inflammasome activation by IFNβ-primed human CD4+CD45RO+ memory T-cells is partly mediated by soluble FasL and is associated with down-regulated P2X7R mRNA expression and reduced response to ATP in monocytes. CD4+CD45RO+ memory T-cells from multiple sclerosis (MS) patients showed a reduced ability to suppress NLRP3 inflammasome activation, however their suppressive ability was recovered following in vivo treatment with IFNβ. Thus, our data demonstrate that human P2X7R-mediated NLRP3 inflammasome activation is regulated by activated CD4+CD45RO+ memory T cells, and provide new information on the mechanisms mediating the therapeutic effects of IFNβ in MS. Memory T-cells were cultured in the presence of monocytes with and without Interferon-beta, resorted and expression profile was determined
2012-12-01 | E-GEOD-35601 | biostudies-arrayexpress
Project description:Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal TCRalphabeta+/CD4+/NKa+/CD8-/+dim T-large granular lymphocyte (LGL) lymphocytosis. Since healthy individuals show (oligo)clonal expansions of hCMV-specific TCRVbeta+/CD4+/cytotoxic/memory T-cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+ T-LGL. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile (GEP) analysis.
2008-09-01 | GSE12488 | GEO
Project description:In healthy individuals, immune control of persistent human cytomegalovirus (HCMV) infection is effectively mediated by virus-specific CD4+ and CD8+ T cells. However, identification of the repertoire of T-cell specificities for HCMV is hampered by the immense protein coding capacity of this betaherpesvirus. We applied a novel approach which employs HCMV deletion mutant viruses, lacking HLA class I immunoevasins. Infection of human fibroblast cell lines with those mutant viruses allowed the direct identification of naturally presented HCMV-derived HLA ligands by mass spectrometry. Using this strategy, we identified 368 unique HCMV-derived HLA class I ligands representing an unexpectedly broad panel of 123 HCMV antigens. Functional characterization revealed memory T-cell responses in seropositive individuals for a substantial proportion (28%) of these novel peptides. The unbiased identification of naturally presented viral epitopes enabled a comprehensive and systematic assessment of the physiological repertoire of anti-HCMV T-cell specificities in seropositive individuals. This approach proved to be superior to procedures applying in silico analysis to identify true viral antigens.
2019-11-20 | PXD013120 | Pride