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Homo sapiens

ABSTRACT: RNA-sequence analyses of four CD4+ T cell subpopulations (PD-1hi CXCR5-, PD-1hi CXCR5+, PD-1lo CXCR5-, and PD-1lo CXCR5+) obtained by culturing in the presence of cytokines.

PROVIDER: PRJDB11669 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	DRR294936.fastq.gz	Fastqsanger.gz
	DRR294937.fastq.gz	Fastqsanger.gz
	DRR294938.fastq.gz	Fastqsanger.gz
	DRR294939.fastq.gz	Fastqsanger.gz
	DRR294940.fastq.gz	Fastqsanger.gz

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Circulating CXCR5+CXCR3+PD-1Lo Tfh-like cells in HIV-1 controllers with neutralizing antibody breadth

Project description:HIV-1-specific broadly-neutralizing antibodies (bnAb) typically develop in individuals with continuous high-level viral replication and increased immune activation, conditions that cannot be reproduced during prophylactic immunization. Understanding mechanisms supporting bnAb development in the absence of high-level viremia may be important for designing bnAb-inducing immunogens. Here, we show that the breadth of neutralizing antibody responses in HIV-1 controllers was associated with a relative enrichment of circulating CXCR5+ CXCR3+ PD-1Lo CD4 T cells. These CXCR3+ PD-1Lo Tfh-like cells were preferentially induced in vitro by functionally superior dendritic cells from controller neutralizers, and able to secrete IL-21 and support B cells. In addition, these CXCR3+ PD-1Lo Tfh-like cells contain higher proportions of stem cell-like memory T cells, and upon antigenic stimulation differentiated into PD-1Hi Tfh-like cells in a Notch-dependent manner. Together, these data suggest that CXCR5+ CXCR3+ PD-1Lo cells represent a dendritic cell-primed precursor cell population for PD-1Hi Tfh-like cells that may contribute to the generation of bnAbs in the absence of high–level viremia.

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Project description:T follicular helper (Tfh) cells, essential for germinal center reactions, are not identical, with different phenotypes reported. Whether, when and how they generate memory cells are still poorly understood. Here, through single-cell RNA-sequencing analysis of CXCR5+Bcl6+ Tfh cells generated under different conditions, we discovered, in addition to PD-1hi effector Tfh cells, a CD62L+PD1low subpopulation. CD62L-expressing Tfh cells developed independently from PD-1+ cells, and not in direct contact with B cells. More importantly, CD62L+ Tfh cells expressed memory- and stemness-associated genes; with more superior long-term survival, they readily generated PD-1hi cells in the recall response. Finally, KLF2 and IL7R, also highly expressed by CD62L+ Tfh cells, were required to regulate their development. Our work thus demonstrates a novel Tfh memory-like cell subpopulation, which may benefit our understanding on immune responses and diseases.

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Project description:CD4+ T-cells from three follicular lymphoma tumors were sorted by flow cytometry into three subsets based on high (hi), intermediate (int), or low (lo) levels of PD-1 and CXCR5 expression and whole genome gene expression profiling was performed. This set contains three samples for PD-1hiCXCR5hiCD4+ T cells, two samples for PD-1intCXCR5intCD4+ T cells, and three samples for PD-1loCXCR5loCD4+ T cells.

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Homo sapiens

Project description:RNA-sequence analyses of PD-1hi CXCR5- Tph cells obtained from PBMC of healthy volunteers or patients with systemic lupus erythematosus.

| PRJDB11670 | ENA

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