Homo sapiens
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PROVIDER: PRJNA131613 | ENA |
REPOSITORIES: ENA
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Project description:Goal: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those related to exosomes. Background: Suppression of human immunodeficiency virus (HIV) replication by CD8+ T-cells (CD8 suppression) contributes to survival in adults and children < 1 year. Soluble CD8 suppression can also be seen in some older children with AIDS. The factor responsible, CD8-derived antiviral factor (CAF), acts at the level of HIV RNA transcription. Differential gene expression techniques have been used to define the gene(s) mediating this phenomenon in adults. Recently, CAF has been linked to exosomes secreted by CD8+ T-cells. Objective: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those reportedly related to exosomes. Design/Methods: We used differential gene expression to study 3 older children with HIV infection, 1 who did demonstrate soluble CD-8 suppression and 2 who did not, and compared our results with those reported in 2 previous studies in adults and their relatedness to exosome components secreted by CD8+ T-cells. Results: 18 differentially expressed genes were also seen in 1 adult study (p=0.002, Ï2 test), and 38 such genes (p < 0.0001, Ï2 test) in a second adult study. In addition, two exosome components and some RNAâs related to exosomal proteins were also differentially expressed. Conclusions: In children with HIV infection, we found significant differentially expressed genes that correlated to those previously reported in 2 studies in adults. Our data also lends some support to the recent identification of CAF with exosomes secreted by CD8+ T-cells. Differential gene expression was used to study 3 older children with HIV infection, 1 who did demonstrate soluble CD-8 suppression and 2 who did not, and compared our results with those reported in 2 previous studies in adults and their relatedness to exosome components secreted by CD8+ T-cells. Three vertically-HIV-1-infected adolescent boys were studied. This study was approved by the Childrenâs Memorial Institutional Review Board. After informed consent was obtained, 20 - 40 ml of heparinized peripheral blood was collected in association with regularly scheduled, clinically-indicated blood sampling. Keywords: differential gene expression; soluble CD8 suppression; gene array; pediatric HIV infection; CD8-derived antiviral factor
2010-10-28 | E-GEOD-23183 | biostudies-arrayexpress
Project description:Goal: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those related to exosomes. Background: Suppression of human immunodeficiency virus (HIV) replication by CD8+ T-cells (CD8 suppression) contributes to survival in adults and children < 1 year. Soluble CD8 suppression can also be seen in some older children with AIDS. The factor responsible, CD8-derived antiviral factor (CAF), acts at the level of HIV RNA transcription. Differential gene expression techniques have been used to define the gene(s) mediating this phenomenon in adults. Recently, CAF has been linked to exosomes secreted by CD8+ T-cells. Objective: To compare the gene expression profiles from pediatric patients with each other, with those reported in adults and in those reportedly related to exosomes. Design/Methods: We used differential gene expression to study 3 older children with HIV infection, 1 who did demonstrate soluble CD-8 suppression and 2 who did not, and compared our results with those reported in 2 previous studies in adults and their relatedness to exosome components secreted by CD8+ T-cells. Results: 18 differentially expressed genes were also seen in 1 adult study (p=0.002, χ2 test), and 38 such genes (p < 0.0001, χ2 test) in a second adult study. In addition, two exosome components and some RNA’s related to exosomal proteins were also differentially expressed. Conclusions: In children with HIV infection, we found significant differentially expressed genes that correlated to those previously reported in 2 studies in adults. Our data also lends some support to the recent identification of CAF with exosomes secreted by CD8+ T-cells.
2010-10-28 | GSE23183 | GEO
Project description:The persistence of HIV infection under ART is due to a reservoir of latently infected cells that harbor replication-competent virus and evade immune recognition. Defining the mechanisms responsible for the establishment and maintenance of HIV latency is crucial to achieve HIV eradication or functional cure. Previous studies demonstrated a non-cytotoxic CD8+ T-cells mediated inhibition of virus replication during untreated HIV/SIV infection and inhibition of virus production under ART; however, the mechanisms responsible for this antiviral effect remained poorly understood. In our primary cell-based in vitro latency model we demonstrated that co-culture with CD8+ T-cells promotes changes in metabolic and cell survival pathways in HIV-infected memory CD4+ T-cells that may negatively regulate HIV expression and ultimately promote the establishment of latency. Modulation of this CD8-mediated activity may represent a tool to disrupt HIV latency and reservoir persistence in ART-treated individuals.
2023-04-27 | GSE198525 | GEO
Project description:The goal of antiretroviral therapy (ART) is to suppress HIV-1-replication and reconstitute CD4-T-cells. Here, we report on HIV-infected individuals, who had a paradoxical decline in CD4-T-cells despite ART-mediated suppression of plasma HIV-1 load (plHIV-1). We defined such immunological outcome as extreme immune decline (EXID).
2020-01-31 | GSE125223 | GEO
Project description:Innate, non-cytolytic CD8+ T cell-mediated suppression of HIV replication by MHC-independent inhibition of virus transcription
| PRJNA539944 | ENA
Project description:CD8+ T-cells provide robust anti-viral immunity, yet how epitope-specific T-cells evolve across the human lifespan is unknown. We defined CD8+ T-cell immunity directed at the prominent influenza epitope, HLA-A*02:01-M158-66 (A2/M158) across four age groups (newborns, children, adults and elderly) ex vivo at phenotypic, single cell sequence (transcriptomic), clonal and functional levels. We identified a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resembled those observed in newborns and children, despite being clonally-different. However, only child- and adult-derived A2/M158+CD8+ T-cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T-cells, which was linked to highly functional public TCRab-signatures. Suboptimal TCRab-signatures detected in older adults led to poorer proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. Our study suggests that priming T-cells at different stages of life might greatly affect CD8+ T-cell responses towards viral infections.
2023-08-16 | GSE237817 | GEO
Project description:CD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is unclear to what extent the viral suppression mediated by CD8+ T-cells reflects direct killing of infected cells as opposed to indirect, non-cytolytic mechanisms. In this study, we used functional genomics to investigate potential mechanisms of in vivo viral suppression mediated by CD8+ lymphocytes. Eight chronically SIVmac239-infected RMs underwent CD8+ lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, at the nadir of CD8+ lymphocytes (5 days post-depletion), and during the repopulation phase (11 days post-depletion). Principal components analysis demonstrated that overall gene expression during the nadir of CD8+ T-cells was highly divergent from other intervals. Conversely, the genomic signature of samples from the CD8+ cell rebound phase was similar to that of pre-depletion samples. During CD8+ lymphocyte depletion we detected a strongly significant decrease in the expression of the genes encoding CD8α and CD8β chains, consistent with the near complete CD8+ T-cell depletion measured by flow cytometry. Of note, we observed significant down-regulation of the expression of genes encoding for factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/Rantes, several retroviral restriction factors (TRIM10, TRIM15, APOBEC3G/H) and defensins. Reduced expression of various genes related to T cell activation and proliferation was also observed. Collectively, these data indicate that depletion of CD8+ lymphocytes in SIV-infected RMs is associated with the establishment of a pattern of gene expression that may result in increased intrinsic permissivity to virus replication. A total of 60 RNA samples were hybridized on to Rhesus Affymetrix 3' Expression arrays. The study was composed of 8 replicate rhesus macaques subjected to SIVmac239 infection and followed over infection, during subsequent treatment with monocloncal antibody OKT8F to deplete CD8+ T lymphocytes, antiretroviral therapy to suppress virus. Samples were taken at various time points during acute and chronic infection, after CD8+ cell depletion, after CD8+ cell reconstition, and during ART suppression of virus.
2013-02-08 | E-GEOD-37834 | biostudies-arrayexpress
Project description:14 children vertically HIV infected ART treated within 6 months of life (ET) and 6 children vertically HIV infected ART treated after 12 months of life were studied to understand the effect of early ART initiation on HIV specific CD4+ T cells and CD8+ T cells functionalities. Additionally, RNAseq on unstimulated PBMC was performed to also evaluate the impact of early ART on the immune transcriptome.
2019-11-13 | GSE138804 | GEO
Project description:HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in all vaccinated macaques following high-dose intravenous challenge by the pathogenic SHIVSF162P3CN. Poly-functional effector-memory CD8+ T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8+ subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8+ T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure.
2021-05-24 | GSE171783 | GEO
Project description:MHC-I-restricted, virus-specific cytotoxic CD8+ T cells control HIV/SIV replication via the recognition and killing of productively infected CD4+ T cells. Several studies in SIV-infected macaques suggest that CD8+ T cells may also decrease virus production by suppressing viral transcription. RNA sequencing is used to identify candidate cellular pathways that are involved in the virus-silencing mediated by these CD8+ T cells.
2020-08-23 | GSE130368 | GEO