Gene expression in CD4 memory T cell responses with age
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mingcan Yu
PROVIDER: E-GEOD-36476 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:With increasing age, the ability of the immune system to protect against recurring infections or to control chronic infections erodes. The objective of the current study was to identify gene expression signatures in elderly CD4 T cell responses
2012-03-14 | GSE36476 | GEO
Project description:BACKGROUND: Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4+ T-cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4+ T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4+ T-cells co-cultured with CD11c+ myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post-integration latent infection in resting CD4+ T-cells, and examined potential cell interactions that may be involved using RNA-seq. RESULTS: mDC (CD1c+), SLAN+ DC and CD14+ monocytes were most efficient in stimulating proliferation of CD4+ T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4+ T-cells following HIV-1 infection of APC-T-cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non-proliferating CD4+ T-cells. Gene expression analysis, comparing the mDC, SLAN+ DC and CD14+ monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4+ T-cells via cell-cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene). CONCLUSIONS: APC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14+ monocytes, were able to efficiently induce post-integration HIV-1 latency in non-proliferating CD4+ T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1 latency may provide novel targets to eliminate HIV latency. mRNA profiles of sorted, pure antigen presenting cells including, CD1c+ myleoid dendirtic cells (mDC), SLAN+ mDC, CD14+ monocytes and plasmacytoid DC (pDC), were generated using next generation sequencing in triplicate, using Illumina Illumina Hiseq 2000.
2015-12-23 | E-GEOD-70106 | biostudies-arrayexpress
Project description:Panton-Valentine Leukocidin (PVL) is a Staphylococcus aureus toxin that binds to and kills human neutrophils resulting in the formation of neutrophil extracellular traps. A subset of individuals colonized with PVL expressing S. aureus suffer from recurring infections. We found that neutrophils from affected individuals display increased spontaneous NET formation after isolation, and increased sensitivity to killing by PVL. Compared to healthy controls, the expression of the target receptors for PVL, CD45 and C5L2, but not CD88, was increased in these patients, and the expression correlated to the amount of PVL-induced NETs produced. NADPH-oxidase activity was not important for PVL induced NETosis as neutrophils from CGD patients produced NETs in response to PVL. Through NET proteome analysis we identified that the protein content of PVL induced NETs is different from mitogen induced NETs. The abundance of the antimicrobial proteins LL37, myeloperoxidase, azurocidin, and proteinase 3 was lower on PVL NETs and PVL-induced NETs were deficient in killing Staphylococcus aureus. Neutrophils from patients that suffer from recurring PVL-positive infections may be more sensitive to PVL-induced NETosis, impairing their ability to combat the infection.
2023-11-23 | PXD025702 | Pride
Project description:BACKGROUND: Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4+ T-cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4+ T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4+ T-cells co-cultured with CD11c+ myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post-integration latent infection in resting CD4+ T-cells, and examined potential cell interactions that may be involved using RNA-seq. RESULTS: mDC (CD1c+), SLAN+ DC and CD14+ monocytes were most efficient in stimulating proliferation of CD4+ T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4+ T-cells following HIV-1 infection of APC-T-cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non-proliferating CD4+ T-cells. Gene expression analysis, comparing the mDC, SLAN+ DC and CD14+ monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4+ T-cells via cell-cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene). CONCLUSIONS: APC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14+ monocytes, were able to efficiently induce post-integration HIV-1 latency in non-proliferating CD4+ T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1 latency may provide novel targets to eliminate HIV latency.
2015-12-23 | GSE70106 | GEO
Project description:Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Myeloid DCs (mDC) were isolated from peripheral blood and co-cultured with conidia (con) and germlings (ks) of Aspergillus fumigatus knockout (mitA, mnt1, rodA) and wildtype (wt) strains for 6 hours at an MOI of 1. RNA was extracted and hybridised to microarrays. Microarrays contain probes for approximately 110 selected human immune-relevant genes, including cytokine and chemokine genes, their receptors and downstream innate immunity genes. We used microarrays to detail the gene expression of human myeloid dendritic cells after 6h of co-cultivation with Aspergillus fumigatus wildtype and knockout mutants
2012-04-16 | E-GEOD-34884 | biostudies-arrayexpress
Project description:Latently infected resting CD4+ T cells are a major barrier to HIV cure. Understanding how latency is established, maintained and reversed is critical to identifying novel strategies to eliminate latently infected cells. We demonstrate here that co-culture of resting CD4+ T cells and syngeneic myeloid dendritic cells (mDC) can dramatically increase the frequency of HIV DNA integration and latent HIV infection in non-proliferating memory, but not naïve, CD4+ T cells. Gene expression in non-proliferating CD4+ T cells, enriched for latent infection, showed significant changes in the expression of genes involved in cellular activation and interferon regulated pathways, including the down-regulation of genes controlling both NF-κB and cell cycle. We conclude that mDC play a key role in the establishment of HIV latency in resting memory CD4+ T cells, which is predominantly mediated through signalling during DC-T cell contact.
2014-11-01 | GSE52344 | GEO
Project description:The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines. 5 donors; 88 samples; duplicate technical replicates for the medium control for each donor for the BDCA1+ mDC population; single medium control for each donor for the BDCA3+ mDC population (15 total medium controls).
2014-10-22 | E-GEOD-56744 | biostudies-arrayexpress
Project description:It has been suggested that CD4+ T cell senescence is involved in the pathogenesis of elderly-onset rheumatoid arthritis (EORA). We performed scRNA-seq analysis using CD4+ T cells collected from inguinal lymph nodes of young and old DBA/1 mice to investigate the association between aging CD4+ T cells and elderly-onset arthritis.
2024-08-19 | GSE263231 | GEO
Project description:Recently, the bone marrow (BM) has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4+ and CD8+ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of naïve and an increase in effector-memory T cells. In contrast to the peripheral blood (PB), a highly activated CD8+CD28– T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation and differentiation of CD8+ T cell in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8+CD28– T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4+ and CD8+ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8+CD28– T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age. A total of 4 samples (bone marrow mononuclear cells) were analyzed (2 young and 2 elderly persons)
2011-10-11 | E-GEOD-32725 | biostudies-arrayexpress
Project description:Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of the genotoxins as effectors during the course of acute and chronic infections remains poorly characterized.To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine chronic infections. Immunocompetent mice were chronically infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional (MC71-TT) or an inactive (MC71-DcdtB) typhoid toxin. Keywords: salmonella typhimurium, bacterial genotoxins, typhoid toxin, chronic infection, mice model Transcriptomic analysis was performed on intestine tissues (colon, jejunum and ileum) and liver collected from 129S6/SvEvTac mice, either uninfected or infected with S. typhimurium MC71 strains (strain MC71-TT, expressing a functional typhoid toxin, and strain MC71-dcdtB, expressing an inactive typhoid toxin) for 60 days
2016-03-31 | E-GEOD-72046 | biostudies-arrayexpress