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Replicative history marks transcriptional and functional disparity in the memory T cell pool

ABSTRACT: Mice received DivisionRecorder+ or unmodified OT-I T cells and were challenged with LM-OVA. During memory phase we FACS sorted memory CD8+ OT-I T cells (and sub-sorted RFP+ and RFP- cells in the case of DivisionRecorder+ cells) from spleen material and performed single cell RNA sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE169154 | GEO | 2021/11/01

REPOSITORIES: GEO

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Replicative history marks transcriptional and functional disparity in the memory T cell pool II

Project description:To validate whether division history is linked to functional and transcriptional properties we established a CTV-based serial-transfer approach that allowes single cell transcriptional profiling of memory T cells that have undergone a high or low amount of prior division

2022-01-31 | GSE184947 | GEO

Replicative history marks transcriptional and functional disparity in the CD8<sup>+</sup> T cell memory pool.

Project description:Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8+ memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that reports the extent of past proliferation of cell pools in vivo. Using this system to genetically 'record' the replicative history of different CD8+ T cell populations throughout a pathogen-specific immune response, we demonstrate that the central memory T (TCM) cell pool is marked by a higher number of prior divisions than the effector memory T cell pool, owing to the combination of strong proliferative activity during the acute immune response and selective proliferative activity after pathogen clearance. Furthermore, by combining DivisionRecorder analysis with single-cell transcriptomics and functional experiments, we show that replicative history identifies distinct cell pools within the TCM compartment. Specifically, we demonstrate that lowly divided TCM cells display enriched expression of stem-cell-associated genes, exist in a relatively quiescent state, and are superior in eliciting a proliferative recall response upon activation. These data provide the first evidence that a stem-cell-like memory T cell pool that reconstitutes the CD8+ T cell effector pool upon reinfection is marked by prior quiescence.

| S-EPMC7612726 | biostudies-literature

Whole-genome microarray analysis of primary, secondary, tertiary and quaternary memory CD8 T cells

Project description:The transcriptome of naive OT-I T cells was compared to memory CD8 T cells after 1, 2, 3, or 4 infection with ovalbumin expressing Listeria monocytogenes (LM-OVA). Naive Thy1.1 OT-I T cells were adoptively transferred into Thy1.2 naive hosts prior to infection with LM-OVA. The resulting memory CD8 T cell population was again adoptively transferred into naive hosts and the recipient mice were again infected with LM-OVA. The adoptive transfer was repeated up to four times to generate memory CD8 T cells with up to four consecutive antigen stimulations. Three individual mice were analyzed for each group. For quaternary memory CD8 T cells, spleens from two to three mice were pooled for each sample. Naive OT-I T cells served as control samples. http://dx.doi.org/10.1016/j.immuni.2010.06.014

2010-07-09 | E-GEOD-21360 | biostudies-arrayexpress

Replicative history marks transcriptional and functional disparity in the memory T cell pool

Project description:Replicative history marks transcriptional and functional disparity in the memory T cell pool

| PRJNA715447 | ENA

Replicative history marks transcriptional and functional disparity in the memory T cell pool II

Project description:Replicative history marks transcriptional and functional disparity in the memory T cell pool II

| PRJNA767084 | ENA

Whole-genome microarray analysis of primary, secondary, tertiary and quaternary memory CD8 T cells

Project description:The transcriptome of naive OT-I T cells was compared to memory CD8 T cells after 1, 2, 3, or 4 infection with ovalbumin expressing Listeria monocytogenes (LM-OVA).

2010-07-10 | GSE21360 | GEO

Comparison of gene expression of OT-I CD8 T cells after infection

Project description:The goal was to examine gene expression after in vivo activation by different vaccine strains of Listeria monocytogenes. Heat killed LM, irradiated LM and live actA- LM were used to immunize mice after transfer of OT-I cells 5x10e5 OT-I-RAG-/- cells transferred to B6 mice, 24hrs later mice immunized; 24hrs later cells sorted on MHC class II-, CD45.1+, CD8+, CD69+ Two arrays were performed per sample for a total of 8 arrays. RAW data file (supplementary file on the Series record) contains the data for each array individually.

2010-06-08 | E-GEOD-20265 | biostudies-arrayexpress

Next-generation sequencing of three memory OT-I cell subsets from mice infected with Listeria monocytogenes

Project description:Purpose: RNA-seq analysis of three memory OT-I cell subsets (from a Klrg1-Cre fate reporter mouse model) isolated from the spleen of C57BL/6 mice infected with Listeria monocytogenes. The hypothesis tested in the present study was that KLRG1+ effector CD8 T lymphocytes differentiate into KLRG1- memory CD8 T lymphocytes and provide long-lasting immunity against infectious diseases and malignancies. Methods: Total RNA was obtained from FACS-purified OT-I cell subsets isolated from spleen 104 (experiment 1) and 110 days post infection (experiment 2) with ovalbumin-expressing Listeria monocytogenes (LM-OVA). Results: Using RNA-seq technology, we performed genome-wide transcriptional profiling of three memory OT-I cells (KLRG1+ Reporter+, KLRG1- Reporter+ (exKLRG1) and KLRG1- Reporter-) and identified 36 genes differentially expressed (> 1.5-fold) between exKLRG1 and KLRG1- Reporter- memory OT-I cells, and 132 differentially expressed genes between exKLRG1 and KLRG1+ Reporter+ memory OT-I cells. We then confirmed the expression of 15 genes/molecules by qRT-PCR and/or flow cytometry. Conclusions: Our study represents the first fate mapping analysis of KLRG1+ effector OT-I cells, demonstrates that KLRG1+ effector OT-I cells differentiate into all memory T cell lineages thereby promoting protective immunity. RNA-seq also identified CX3CR1 as a marker of circulating exKLRG1 early memory OT-I cells.

2018-03-01 | GSE110629 | GEO

Gene expression profile of CD8+ T cell subtypes

Project description:OT-I naïve T cells, central memory T cells, effector memory T cells and skin infiltrating T cells were sorted out from mice at different timepoints post infection OT-I cells from 15-20 mice were pooled together for each microarray dataset

2017-02-21 | GSE79805 | GEO

Next Generation Sequencing Facilitates Quantitative Analysis of WT and Il2ra mut/mut memory OT-I cell transcriptomes

Project description:Cognate antigen signals control CD8+ T cell priming, expansion size and effector versus memory cell fates, however, it is not clear whether they can also modulate the functional features of memory CD8+ T cells. We observed that OT-I cells that were primed with weak cognate antigen signals incorporate more cytokine signals, leading to a hypothesis that CD8+ T cells that receive weak TCR signals require cytokine signals to form functional memory. Using a previously described mouse model in which IL-2 signaling via its high affinity receptor CD25 is selectively impaired, the “Il2ramut/mut” mouse, we conducted a comparative analysis of gene expression and epigenetic landscape of Il2ramut/mut and WT OT-I memory cells that were primed with strong (Lm-Ova N4) versus weak (Lm-Ova T4). RNA seq data showed that both TCR and IL-2 priming signals have minimal effect on gene expression in resting memory CD8 T cells, but they significantly modify the epigenetic landscape of the memory CD8 T cells. These findings have important contributions to the current understanding of how priming signals program memory CD8 T cells in vivo.

2020-09-30 | GSE152393 | GEO

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