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Effector CD8 T cells dedifferentiate into long-lived memory cells

ABSTRACT: Effector CD8 T cells dedifferentiate into long-lived memory cells

PROVIDER: PRJNA419196 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6309592.fastq.gz	Fastqsanger.gz
	SRR6309592_1.fastq.gz	Fastqsanger.gz
	SRR6309592_2.fastq.gz	Fastqsanger.gz
	SRR6309593.fastq.gz	Fastqsanger.gz
	SRR6309593_1.fastq.gz	Fastqsanger.gz

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Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells

Project description:Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells

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Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells

Project description:Memory T cells are critical for vaccines and T-cell-based therapies. However, the differentiation path of memory T cells is not completely understood. Early bulk cell population-based studies support a linear model, in which effector T cells lose the effector program and dedifferentiate into memory T cells. Recent research supports a bifurcation model, where T cells choose one of the two paths, either the effector or the memory path, at an early stage of T cell responses. Terminal effector T cells lose the capacity to become memory T cells. Here, we first demonstrate that the expression of granzyme A is largely distinct from that of granzyme B and marks terminal cytotoxic effector CD8+ T cells with reduced polyfunctionality. Using a granzyme A-fate mapping mouse line and an acute viral infection model, we discovered that early memory T cells are largely derived from cells lacking a history of granzyme A expression, supporting the bifurcation model. Progressively, granzyme A-expressing terminal effector T cells dedifferentiate into functional long-term memory T cells. At the late memory phase, memory T cells are a mixed population composed of cells with different differentiation paths (i.e., the linear and the bifurcated paths) that coordinate to provide balanced immune protection.

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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

Effector CD8 T cells dedifferentiate into long-lived memory cells.

Project description: Not available

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Effector CD8 T cells dedifferentiate into long-lived memory cells

Project description:DNA methyltransferase 3a regulates CD8 T cell memory differentiation

2017-12-16 | GSE107150 | GEO

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

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

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Influenza-specific effector memory B cells predict long-lived antibody responses to vaccination in humans

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CHD7 promotes anti-viral short-lived effector CD8+ T cells

Project description:CD8+ T cells differentiate into two subpopulations in response to acute viral infection: memory precursor effector cells (MPECs) and short-lived effector cells (SLECs). MPECs and SLECs are epigenetically distinct; however, the epigenetic regulators required for formation of these subpopulations are mostly unknown. Here we performed an in vivo CRISPR screen in murine naive CD8+ T cells to identify the epigenetic regulators required for MPEC and SLEC formation, using the acute lymphocytic choriomeningitis virus (LCMV) Armstrong infection model. We identified the ATP-dependent chromatin remodeler chromodomain-helicase-DNA-binding-protein-7 (CHD7) as a positive regulator of SLEC formation, as knockout (KO) of Chd7 reduced SLECs numerically. In contrast, KO of Chd7 increased the formation of central memory T cells following pathogen clearance yet attenuated memory cell expansion following a rechallenge. These findings establish CHD7 as a novel positive regulator of SLEC and negative regulator of central memory T cell formation.

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Transcription profiling of human CD8 naive (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells

Project description:Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naïve (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of TN and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.

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CHD7 promotes anti-viral short-lived effector CD8+ T cells [RNA-seq]

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