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Single-cell analysis of adipose tissue T cells in diabetic persons with HIV reveals high proportions of clonally expanded CMV-like CD4+ T cells with cytotoxic RNA transcriptomes

ABSTRACT: Single-cell analysis of adipose tissue T cells in diabetic persons with HIV reveals high proportions of clonally expanded CMV-like CD4+ T cells with cytotoxic RNA transcriptomes

PROVIDER: PRJNA670431 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12879200.fastq.gz	Fastqsanger.gz
	SRR12879201.fastq.gz	Fastqsanger.gz
	SRR12879202.fastq.gz	Fastqsanger.gz
	SRR12879203.fastq.gz	Fastqsanger.gz
	SRR12879204.fastq.gz	Fastqsanger.gz

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Single-cell analysis of adipose tissue T cells in diabetic persons with HIV reveals high proportions of clonally expanded CMV-like CD4+ T cells with cytotoxic RNA transcriptomes

Project description:Persons with HIV have a disproportionate burden of metabolic disease, including type 2 diabetes. We hypothesized that the accumulation of chronically activated T cells in the adipose tissue of HIV+ persons is a central mechanism promoting local macrophage activation, impaired adipocyte function, and the development of HIV-associated glucose intolerance. Prior studies of immune activation and HIV-associated metabolic disease have only measured circulating T cell subsets. In contrast, in our study we recruited a longitudinal cohort of HIV+ patients on antiretroviral therapy ranging from insulin sensitive to overtly diabetic, in addition to HIV-negative diabetic controls, to identify potential mechanistic linkages between adipose-resident T cell cytokine signaling, adipose tissue inflammation, and glucose intolerance in HIV+ persons. This study may also provide further insight into the role of T cells in the development of glucose intolerance in HIV-negative patients.

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Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [CSF]

Project description:Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which neuroinflammation plays a critical function. Recurring viral infections and loss of immune competence increase risk for developing AD, yet the cellular and molecular mechanisms driving these immune changes are unknown. Here we performed mass cytometry of peripheral blood mononuclear cells and detected an immunologic signature of AD characterized by increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. CD8+ TEMRA cells were negatively associated with cognition and single cell RNA sequencing revealed their cytotoxic effector function. Strikingly, we discovered identical, shared T cell receptors (TCRs) of clonally expanded CD8+ TEMRA cells in cerebrospinal fluid (CSF) of three AD patients. Deep TCR sequencing, machine learning, and peptide screens identified the HLA-B*08:01-restricted Epstein-Barr virus trans-activator protein BZLF1 as the cognate antigen of a novel AD CSF TCR . These results provide the first evidence of clonal, antigen-specific T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration

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