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Transcriptional basis of CD4 T cel help for memory CD8 T cell formation

ABSTRACT: Transcriptional basis of CD4 T cel help for memory CD8 T cell formation

PROVIDER: PRJNA557502 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9864970.fastq.gz	Fastqsanger.gz
	SRR9864961.fastq.gz	Fastqsanger.gz
	SRR9864971.fastq.gz	Fastqsanger.gz
	SRR9864962.fastq.gz	Fastqsanger.gz
	SRR9864972.fastq.gz	Fastqsanger.gz

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Epigenetic basis of CD4 T cel help for memory CD8 T cell formation

Project description:Epigenetic basis of CD4 T cel help for memory CD8 T cell formation

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Transcriptional basis of CD4 T cel help for memory CD8 T cell formation

Project description:CD4+ T-cell help is required for the generation of CD8+ cytotoxic T lymphocyte (CTL) memory. We here reveal how “help” signals delivered during priming impact memory differentiation of CTLs, as informed by genome-wide analyses. “Help” signals promoted the IL-15-dependent maintenance of central memory (TCM) cells. However, they had a much larger impact on the generation of effector memory (TEM) cells and their gene expression program . CD4+ T-cell help created TEM cells that produced Granzyme B and IFNg after antigen-independent recall with IL-12 and IL-18. Furthermore, “helped” memory CTLs expressed the effector program characteristic of “helped” primary CTLs upon recall with MHC class I-restricted antigen only, due to both epigenetic imprinting and sustained mRNA expression of relevant genes . Thus, CD4+ T-cell help delivered during priming creates CD8+ TEM cells with innate and help-independent recall capacities.

2019-10-23 | GSE135141 | GEO

Epigenetic basis of CD4 T cel help for memory CD8 T cell formation

Project description:We report here the effects of CD4 T cell help during priming on the acquistion of specific epigenetic program by memory CD8 T cells.

2019-10-23 | GSE118159 | GEO

CD4+ T-cell help creates effector memory CTLs with innate and help-independent recall capacities

Project description:CD4+ T-cell help creates effector memory CTLs with innate and help-independent recall capacities

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Memory CD4 T cells help adaptive immunity with minimal immunopathology

Project description:CD4 T cells play critical roles in promoting inflammation and helping immune responses, but knowledge of how memory CD4 T cells are regulated and how they help adaptive immune responses is limited. Using adoptive transfer of virus-specific CD4 T cells, we show that naïve CD4 T cells undergo substantial expansion following viral infection, but can induce lethal TH1-driven inflammation. In contrast, memory CD4 T cells exhibit a biased proliferation of T follicular helper (Tfh) cell subsets that correlate with improved adaptive responses and minimal tissue damage following viral infection. Importantly, our analyses revealed that type I interferon regulates the expansion of naïve CD4 T cells, but does not seem to play a critical role in regulating the expansion of memory CD4 T cells. Moreover, blockade of type I interferon signaling abrogated lethal CD4 T cell inflammation following viral infection. Taken together, these data demonstrate a previously undescribed function for memory CD4 T cells: to help adaptive immunity with minimal harm to the host. These findings are important for rational vaccine design and for improving the safety and efficacy of adoptive T cell therapies against persistent antigens. Primary and memory SMARTA cells were MACS-purified by negative selection (STEMCELL) and then FACS-sorted to 98% purity on a FACS Aria (BD Biosciences) according to congenic marker expression (CD45.1+ for secondary, and CD45.1+ CD45.2+ for primary, CD4 T cell responses).

2017-03-31 | GSE92474 | GEO

The molecular basis of CD4 T-cell help for the cytotoxic T-cell response

Project description:CD4+ T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes, resulting from CD4+ T-cell help during priming, as apparent in effector CTLs. This gene expression signature reveals that CD4+ T-cell help optimizes CTLs in the expression of cytotoxic effector molecules, but also in many other functions that ensure optimal efficacy of CTLs throughout their life cycle.

2017-11-07 | GSE89665 | GEO

Subregion-specific proteomic signature in the hippocampus for memory formation in adult mice

Project description:The hippocampal formation is a brain structure essential for higher-order cognitive functions. It has exquisite differences in anatomical organization and cellular composition, and hippocampal sub-regions have different properties and functional roles. Areas CA1 and CA3 in particular, are key sub-regions for learning and memory formation that fulfill complementary but specific functions. The molecular basis for such specific properties and the link to learning and memory remain unknown. Here using a SWATH-MS proteomic approach and bioinformatic tools, we identify a selective proteomic signature in area CA1 and CA3, and reveal their specific dynamics during memory formation. We show that 30% of all quantifiable proteins are differentially expressed in area CA1 and CA3 at baseline, and that each proteome responds differently during the formation of memory for object or object location. Using clustering and cross-correlational analyses, we outline specific temporal proteomic profiles and an increased correlation between both forms of memory within area CA1, but not within area CA3. These results provide new insight into a proteomic basis for hippocampal sub-region molecular and functional specificity.

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Human Extrafollicular CD4+ T Helper Cells Help Memory B Cells Produce Immunoglobulins

Project description:Follicular helper T (Tfh) cells are necessary for germinal center B cell maturation during primary immune responses; however, the T cells that promote humoral recall responses via memory B cells are less well defined. We herein characterize a human tonsillar CD4+ T cell subset with this function. These cells are similar to Tfh cells in terms of expression of the chemokine receptor CXCR5 and the inhibitory receptor PD-1, interleukin (IL)-21 secretion, and expression of the transcription factor BCL6; however, unlike Tfh cells that are located within the B cell follicle and germinal center, they reside at the border of the T cell zone and the B cell follicle in proximity to memory B cells, a position dictated by their unique chemokine receptor expression. They promote memory B cells to produce antibodies via CD40 ligand, IL-10, and IL-21. Our results reveal a unique extrafollicular CD4+ T cell subset in human tonsils, which specialize in promoting T cell-dependent humoral recall responses.

2018-06-29 | GSE52156 | GEO

Proliferation-competent Tcf1+ CD8 T-cells in dysfunctional populations are CD4 T-cell help independent

Project description:Effector CD8 T-cell responses in chronic infection and cancer are maintained by proliferation competent progenitors, which share features with the progenitors of memory T-cells in acutely resolved infections. Combining classical assessment of population dynamics with single cell RNA-sequencing, we discovered a switch in the need for CD4 help between related populations in acute and chronic infection. While in acute infection memory T-cells but not effector T-cells are CD4 help dependent, we found the opposite in chronic infection. Thus, progenitor cells in chronic infection acquire a level of autonomous function that is not seen among their counterparts in acute infection. Vice versa, the dependece of the effector cells highlight why a functional antigen-specific CD4 T-cell compartment is critical in therapeutic settings.

2019-09-11 | GSE137007 | GEO

Single cell RNAseq analysis of anti-Vaccinia long-lived memory B cells (CEL-seq2)

Project description:Single cell RNAseq analysis of anti-Vaccinia long-lived memory B cells (CEL-seq2)

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