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KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate Into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity

ABSTRACT: KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate Into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity

PROVIDER: PRJNA434329 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6727442.fastq.gz	Fastqsanger.gz
	SRR6727443.fastq.gz	Fastqsanger.gz
	SRR6727444.fastq.gz	Fastqsanger.gz
	SRR6727445.fastq.gz	Fastqsanger.gz
	SRR6727446.fastq.gz	Fastqsanger.gz

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KLRG1<sup>+</sup> Effector CD8<sup>+</sup> T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity.

Project description:Protective immunity against pathogens depends on the efficient generation of functionally diverse effector and memory T lymphocytes. However, whether plasticity during effector-to-memory CD8+ T cell differentiation affects memory lineage specification and functional versatility remains unclear. Using genetic fate mapping analysis of highly cytotoxic KLRG1+ effector CD8+ T cells, we demonstrated that KLRG1+ cells receiving intermediate amounts of activating and inflammatory signals downregulated KLRG1 during the contraction phase in a Bach2-dependent manner and differentiated into all memory T cell linages, including CX3CR1int peripheral memory cells and tissue-resident memory cells. "ExKLRG1" memory cells retained high cytotoxic and proliferative capacity distinct from other populations, which contributed to effective anti-influenza and anti-tumor immunity. Our work demonstrates that developmental plasticity of KLRG1+ effector CD8+ T cells is important in promoting functionally versatile memory cells and long-term protective immunity.

| S-EPMC6465538 | biostudies-literature

KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate Into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-03-01 | GSE110707 | GEO

RNA-sequencing of three murine memory CD8 T cell subsets: IL-7Rα+KLRG1- , IL-7Rα+KLRG1+, and IL-7Rα-KLRG1+

Project description:The goal of this study is to characterize the transcriptional profile of three memory CD8 T cell subsets: IL-7Rα+KLRG1- (memory precursors, MP), IL-7Rα+KLRG1+ (KLRG1+ MP) and IL-7Rα-KLRG1+ (terminal effectors, TE).

2022-12-12 | GSE218777 | GEO

PD-1 regulates KLRG1+ group 2 innate lymphoid cells

Project description:Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens, allergens, tissue remodeling and metabolic homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated but co-receptor mediated negative regulatory axis is yet to be defined. We demonstrate that PD-1 is an important negative regulator of KLRG1+ILC-2 function in both mice and humans. Increase in KLRG1+ ILC-2 cells numbers were attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred in pdcd1-/- mice and on adoptive transfer, pdcd1-/- KLRG1+ ILC-2s significantly reduced worm burden. Furthermore, blocking antibody to PD-1 increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore PD-1 is an important negative regulator and is vital for maintaining the number and hence function of KLRG1+ ILC-2s.

2017-05-04 | GSE94609 | GEO

KLRG1 and NKp46 discriminate subpopulations of human CD117+ CRTH2- ILCs biased toward ILC2 or ILC3

Project description:Recently, circulating multi- and uni-potential human ILC precursors (ILCP) have been found in a lymphocyte population that expresses CD117 and CD127 but lack CRTH2 and NKp44. However, these ILCPs have not been extensively characterized. We performed an unbiased Hierarchical Stochastic Neighbor Embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCPs which revealed the presence of three major subsets; the first expressed NKp46, the second expressed both NKp46 and CD56 and the third expressed KLRG1. Analysis of the differentiation potential of these cells on bulk and clonal levels, cytokine production and the transcriptome revealed that the NKp46+ ILCPs contain high frequencies of ILC3 precursors whereas a minority can differentiate into ILC1/NK-like cells. In contrast KLRG1+ ILCPs are biased to the ILC2 lineage, but are highly plastic and epigenetically poised to differentiate to other ILC subsets depending on the activation signals they receive.

2019-06-05 | GSE123817 | GEO

KLRG1 and NKp46 expressing CD117+ human innate lymphoid cell precursors are biased to ILC2 and ILC3, respectively

Project description:Recently, circulating multi- and uni-potent human ILC precursors (ILCP) have been found in a lymphocyte population that expresses CD117 and CD127 but lacks CRTH2 and NKp44. However, these ILCPs have not been extensively characterized. We performed an unbiased Hierarchical Stochastic Neighbor Embedding (HSNE) analysis of the phenotype of peripheral blood CD117+ ILCPs which revealed the presence of three major subsets: the first expressed NKp46, the second expressed both NKp46 and CD56, while the third expressed KLRG1. Analysis of their differentiation potential on bulk and clonal levels, cytokine production and the transcriptome revealed that the NKp46+ ILCPs contain high frequencies of ILC3 precursors whereas a minority can differentiate into ILC1/NK-like cells. In contrast, KLRG1+ ILCPs are biased to the ILC2 lineage, but are highly plastic and epigenetically primed to differentiate into other ILC subsets depending on the activation signals they receive.

2019-06-05 | GSE124054 | GEO

RNA-sequencing of three murine memory CD8 T cell subsets: IL-7Rα+KLRG1- , IL-7Rα+KLRG1+, and IL-7Rα-KLRG1+

Project description:RNA-sequencing of three murine memory CD8 T cell subsets: IL-7Rα+KLRG1- , IL-7Rα+KLRG1+, and IL-7Rα-KLRG1+

| PRJNA905436 | ENA

KLRG1+ Memory CD8 T cells Combine Properties of Short-lived Effectors and Long-lived Memory

Project description:CD8 effector T cells with a CD127hi KLRG1- phenotype are considered precursors to the long-lived memory pool, while KLRG1+ CD127low cells are viewed as short-lived effectors. Nevertheless, we and others have shown that a KLRG1+ CD127low population persists into the memory phase and that these T cells (termed long-lived effector cells or LLEC) display robust protective function during acute re-challenge with bacteria or viruses. Whether these T cells represent a true memory population or are instead a remnant effector cell population that failed to undergo initial contraction has remained unclear. Here, we show that LLEC from mice express a distinct phenotypic and transcriptional signature that shares characteristics of both early effectors and long-lived memory cells. Furthermore, we find that LLEC are exclusively derived from day 12 KLRG1+ effector cells. Our work challenges the concept that the KLRG1+ CD127low population is dominated by short-lived cells and shows that KLRG1 downregulation is not a prerequisite to become a long-lived protective memory T cell.

2020-08-26 | GSE152841 | GEO

Functional separation of IL7Rα/KLRG1-defined CD8+ T cell populations in humans

Project description:During acute viral infections in mice, IL-7Rα and KLRG1 together are used to distinguish the short-lived effector cells (SLEC; IL-7RαloKLRGhi) from the precursors of persisting memory cells (MPEC; IL-7RαhiKLRG1lo). We here show that these markers can be used to define distinct subsets in the circulation and lymph nodes during the acute phase and in ‘steady state’ in humans. In contrast to the T cells in the circulation, T cells derived from lymph nodes hardly contain any KLRG1-expressing cells. The four populations defined by IL-7Rα and KLRG1 differ markedly in transcription factor, granzyme and chemokine receptor expression. When studying renal transplant recipients experiencing a primary hCMV and EBV infection, we also found that after viral control, during latency, Ki-67-negative SLEC can be found in the peripheral blood in considerable numbers. Thus, combined analyses of IL-7Rα and KLRG1 expression on human herpes virus-specific CD8+ T cells can be used to separate functionally distinct subsets in humans. As a non-cycling IL-7RαloKLRG1hi population is abundant in healthy humans, we conclude that this combination of markers not only defines short-lived effector cells during the acute response but also stable effector cells that are formed and remain present during latent herpes infections.

2019-02-01 | GSE113098 | GEO

Expansion of polyfuntional CD57+ KLRG1+ senescent CD4+ and CD8+ T cells in breast cancer patients.

Project description:We used microarrays to compare the gene expression profile of DP and DN (KLRG1 and CD57) CD4+ T cells from luminal breast cancer patients and healthy donors.

2021-08-18 | GSE142080 | GEO

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