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Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

ABSTRACT: Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

PROVIDER: PRJNA967034 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24423600_1.fastq.gz	Fastqsanger.gz
	SRR24423600_2.fastq.gz	Fastqsanger.gz
	SRR24423601_1.fastq.gz	Fastqsanger.gz
	SRR24423601_2.fastq.gz	Fastqsanger.gz
	SRR24423602_1.fastq.gz	Fastqsanger.gz

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Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

Project description:Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

| PRJNA962490 | ENA

Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

Project description:Mechanisms by which HIV causes susceptibility to respiratory pathogens remain incompletely understood. We obtained whole blood and bronchoalveolar lavage (BAL) from people with latent TB infection in the presence or absence of ARV-naïve HIV co-infection. Transcriptomic and flow cytometric analyses demonstrated HIV-associated cell proliferation and type I interferon activity in blood and effector memory CD8 T-cells in BAL. Both compartments displayed reduced induction of CD8 T cell-related IL-17A in people with HIV, associated with elevated T cell regulatory molecule expression. We propose dysfunctional CD8 T cell responses in uncontrolled HIV contribute to susceptibility to secondary bacterial infections, including tuberculosis.

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Dysfunctional effector memory CD8 T cells in the bronchoalveolar compartment of people living with HIV

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DNA methylation demonstrates bronchoalveolar cell senescence in people living with HIV: An observational cohort study

Project description:DNA methylation demonstrates bronchoalveolar cell senescence in people living with HIV: An observational cohort study

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DNA methylation demonstrates bronchoalveolar cell senescence in people living with HIV: An observational cohort study

Project description:Background: Age-related comorbidities remain a burden in People living with HIV (PLWH). DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. Here, we investigate whether bronchoalveolar lavage (BAL) cells of PLWH demonstrate epigenome wide disruptions and advanced epigenetic aging. Methods: BAL cell DNA methylation profiles from 25 PLWH and 16 uninfected controls were tested for differential methylation of transposable elements Alu and LINE-1, a marker of aging. We used a weighted gene correlation network analysis to identify co-methylation networks associated with HIV and age. We tested the effect of HIV on DNA methylation using a robust linear model. An enrichment analysis was conducted to identify differentially methylated pathways (false discovery rate <0.10). Results: The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways associated with HIV, Ras signaling, T cell receptors, and bacterial invasion of epithelial cells. We identified 6,428 differentially methylated sites associated with HIV. Conclusions: We have shown here for the first time that alterations in the DNA methylation of BAL cells (mainly macrophages) in the lung HIV show in a pattern of advanced aging. In conjunction with our findings in blood cells and airway cells, this study strongly support that HIV may contribute to increase the risk of lung comorbidities through the epigenetic regulation of aging.

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Project description:Immune activation in people living with HIV on anti-retroviral therapy is associated with increased risk of morbidity and mortality, but the underlying mechanisms are poorly understood. To identify whether perturbation of immunological pathways persist at systems level, we compared genome-wide whole blood transcriptomes from 26 people living with HIV on long-term anti-retroviral therapy with 12 HIV-negative healthy controls. All participants were Caucasian male adults recruited from London, UK. People living with HIV were on anti-retroviral therapy for a median of 8.5 years (interquartile range 3-16 years). They had undetectable plasma HIV viral load (<40 copies/ml) and median circulating CD4 counts of 703 cells/µl (interquartile range 491-841 cells/µl).

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Project description:Genome-wide DNA methylation profiling of blood samples from people living with HIV HIV-1 infection impacts biological ageing, and epigenetic clocks highlight epigenetic age acceleration in people with HIV. Despite evidence indicating sex differences in clinical, immunological, and virological measures, females have been underrepresented in most HIV epigenetic studies. Hence, we generated a more representative epigenetic dataset to examine sex differences in epigenetic ageing and relationships to clinical phenotypes.

2025-03-05 | GSE283506 | GEO

Blood plasma from people living with HIV-1 or HIV-2

Project description:In this study we performed data-independet mass-spectrometry analysis of blood plasma collected from a cohort consisting of people living with HIV-1, people living with HIV-2, and HIV seronegative individuals. The data was used to infer signs of damage to a wide array of tissues and cell types.

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Gene expresison of effector and exhausted CD8+ T cells from viremic people living with HIV

Project description:The differential expression of metabolic genes between effector and exhausted CD8+ Tcells has been characterized in the people living with HIV (PLWH) using 768 genes from the NanoString Human Metabolic Pathways Panel.

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Dysfunctional CD8+ T cells form a proliferative, dynamically regulated compartment within human melanoma [scRNA-seq]

Project description:Tumor immune cell compositions play a major role in response to immunotherapy but the heterogeneity and dynamics of immune infiltrates in human cancer lesions remain poorly characterized. Here we identify conserved intratumoral CD4 and CD8 T cell behaviors in scRNA-seq data from 25 melanoma patients. We discover a large population of CD8 T cells showing continuous progression from an early effector “transitional” into a dysfunctional T cell state. CD8 T cells that express a complete cytotoxic gene set are rare, and TCR sharing data suggest their independence from the transitional and dysfunctional cell states. Notably, we demonstrate that dysfunctional T cells are the major intratumoral proliferating immune cell compartment and that the intensity of the dysfunctional signature is associated with tumor-reactivity. Our data demonstrate that CD8 T cells previously defined as exhausted, are in fact a highly proliferating, clonal and dynamically differentiating cell population within the human tumor microenvironment.

2018-12-27 | GSE123139 | GEO

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