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Defining heterogeneity and biological signature in human effector memory CD8+ T cells expressing different levels of IL-7 receptor alpha by high-dimensional analysis

ABSTRACT: FACS-purified human effector memory (EM) CD8+ T cells were analyzed for single cell gene expression profile using single cell RNA-seq. The relationship of IL-7 receptor alpha expression with other molecules was determined at the single cell level. The results showed heterogeneity in human EM CD8+ T cells as defined by IL-7Ra expression that has distinct but organized relationships with a set of molecules, including effector molecules, chemokine receptors, and transcription factors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133167 | GEO | 2019/12/31

REPOSITORIES: GEO

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IL-6R identifies early differentiated human effector memory CD8+ T cells that potently expand and produce IL-2 and IL-13

Project description:We found a unique subset of effector memory (EM) CD8+ T cells that expressed high levels of IL-6 receptor in human peripheral blood. These cells which also expressed high levels of IL-7Ra (referred to as IL-6R high IL-7Rahigh cells) had the a distinct gene expression profile and cellular characteristics compared to other EM CD8+ T cells. IL-6R high IL-7Ra high cells were early differentiated EM CD8+ T cells with decreased expression of T-bet, KLRG1, perforin and granzyme B. These cells had increased cell proliferation likely secondary to enhanced IL-2 production and high affinity IL-2R expression. IL-6R high IL-7Ra high EM CD8+ T cells exclusively produced high levels of IL-2, IL-5, IL-9 and IL-13 although IFN-r was produced by this cell subset and other EM CD8+ T cells. Of interest, IL-6R high IL-7Ra high EM CD8+ T cells expanded in the peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and asthma where CD8+ T cells, IL-13 and IFN-r are suggested to be involved in the pathogenesis. Being the early-differentiated EM CD8+ T cells with a potent capacity to proliferate, survive and generate multiple cytokines, IL-6R high IL-7Ra high EM CD8+ T cells may serve as a primary reservoir for effector CD8+ T cells which potently expand and produce cytokines upon immune stimulation. Duplicate experiments were performed for each condition. In each condition, we independently prepared total RNA using the RNeasy mini kit (Qiagen) and assessed RNA integrity using Bioanalyzer 2100 (Agilent)- RINs were close to 10 for all samples. RNA was then amplified and hybridized to the Illumina HumanHT-12 v4.0 BeadChip, according to Illumina standard protocols.

2012-12-31 | E-GEOD-34562 | biostudies-arrayexpress

IL-6R identifies early differentiated human effector memory CD8+ T cells that potently expand and produce IL-2 and IL-13

2012-12-31 | GSE34562 | GEO

Differentially methylated genes in human IL-7Ra high and low EM CD8+ T cells

Project description:Genome wide DNA methylation profiling of IL-7Ra high and low EM CD8+ T cells. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,578 CpGs. Samples included 2 IL-7Ra high EM CD8+ T cells and 2 IL-7Ra high EM CD8+ T cells.

2015-08-06 | GSE67816 | GEO

Differentially methylated genes in human IL-7Ra high and low EM CD8+ T cells

2015-08-06 | E-GEOD-67816 | biostudies-arrayexpress

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Project description:It is known that human IL-7R low and high EM CD8+ T cells have a difference in the expression of some co-stimulatory, effector and cytotoxic molecules. However, their global gene expression profiles have not been characterized. We thus analyzed global gene expression by IL-7R low and high EM CD8+ T cells in healthy human peripheral blood.

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Project description:We investigated the entity of IL-7Rα low effector memory (EM) CD8+ T cells in healthy individuals and finally uncovered that they were unable to proliferate and produce IL-2 in response to TCR stimulation

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Project description:The generation of CD8+ T-cell memory is an important aim of immunization. While several distinct subsets of CD8+ T-cell memory have been described, the lineage relationships between effector (EFF), effector memory (EM) and central memory (CM) T cells remain contentious. Specifically, there is contradictory experimental evidence to support both the linear (Naive>EFF>EM>CM) and progressive differentiation (Naive>CM>EM>EFF) models. In this study, we applied a systems biology approach to examine global transcriptional relationships between the three major CD8+ T cell subsets arising endogenously as a result of vaccination with three different prime-boost vaccine regimens. Differential gene expression analysis and principle component analysis revealed that central memory cells were more closely related to naive T cells than both effector memory and effector cells. When the transcriptional relationships between subsets were enriched in an unbiased fashion with known global transcriptional changes that result when T-cells repeatedly encounter antigen, our analysis favored a model whereby cumulative antigenic stimulation drives differentiation specifically from Naive > CM > EM > EFF. These findings provide an insight into the lineage relationship between mature CD8+ T-cell subsets and will help in the rational design of vaccines aimed at generating effective immune responses against infections and cancer. Effector (EFF), effector memory (EM), central memory (CM) and naive CD8+ T cells from mice spleen. Memory subset arise endogenously as a result of vaccination with three different prime-boost vaccine regimens: DNA-rAd5, rAd5-rAd5 and rAd5-rLCMV.

2013-08-01 | E-GEOD-42459 | biostudies-arrayexpress

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