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The fate of CD8+ T cells during infection is linked to their developmental origin [Virtual_Memory_following_infection_timestamp]

ABSTRACT: During immune ontogeny the thymus is colonized by distinct waves of hematopoietic stem cells that give rise to unique lineages of immune cells. In this report, we asked whether the developmental origin of CD8+ T cells influences their response to infection later in adulthood. To answer this question, we developed a system to ‘timestamp’ CD8+ T cells in situ at various stages of development (1d and 28d) and examined their behavior after thymic differentiation. We found that neonatal-derived CD8+ T cells have an intrinsic propensity to become virtual memory cells prior to infection and are the first cells to proliferate and become effectors after microbial challenge. These data indicate that there are developmental layers in the adult CD8+ T cell response to infection and that the heterogeneity in the effector pool is linked to the variation in the developmental origins of the responding cells. This dataset profiles gene expression in 1day- and 28day-timestamped virtual memory (CD44hi) CD8+ T cells aged for 4 weeks of post-thymic differentiation and then transferred into congenically marked recipients. Timestamped cells were recovered 5 days following infection with Listeria monocytogenes.

ORGANISM(S): Mus musculus

PROVIDER: GSE109754 | GEO | 2018/06/14

REPOSITORIES: GEO

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The fate of CD8+ T cells during infection is linked to their developmental origin [VirtualMemory_and_TrueNaïve_timestamp]

Project description:During immune ontogeny the thymus is colonized by distinct waves of hematopoietic stem cells that give rise to unique lineages of immune cells. In this report, we asked whether the developmental origin of CD8+ T cells influences their response to infection later in adulthood. To answer this question, we developed a system to ‘timestamp’ CD8+ T cells in situ at various stages of development (1d and 28d) and examined their behavior after post-thymic differentiation. We found that neonatal-derived CD8+ T cells have an intrinsic propensity to become virtual memory cells prior to infection and are the first cells to proliferate and become effectors after microbial challenge. These data indicate that there are developmental layers in the adult CD8+ T cell response to infection and that the heterogeneity in the effector pool is linked to the variation in the developmental origins of the responding cells. This dataset profiles gene expression in 1day- and 28day-timestamped virtual memory (CD44hi) and "true naive" (CD44 lo) CD8+ T cells in cells that had undergone the same amount of post-thymic maturation (4 weeks, transgenic mice, different sorts).

2018-06-14 | GSE109753 | GEO

The fate of CD8+ T cells during infection is linked to their developmental origin [VirtualMemory_and_TrueNaïve_timestamp_ATACseq]

Project description:During immune ontogeny the thymus is colonized by distinct waves of hematopoietic stem cells that give rise to unique lineages of immune cells. In this report, we asked whether the developmental origin of CD8+ T cells influences their response to infection later in adulthood. To answer this question, we developed a system to ‘timestamp’ CD8+ T cells in situ at various stages of development (1d and 28d) and examined their behavior after post-thymic differentiation. We found that neonatal-derived CD8+ T cells have an intrinsic propensity to become virtual memory cells prior to infection and are the first cells to proliferate and become effectors after microbial challenge. These data indicate that there are developmental layers in the adult CD8+ T cell response to infection and that the heterogeneity in the effector pool is linked to the variation in the developmental origins of the responding cells. This dataset profiles chromatin accessibility in 1day- and 28day-timestamped virtual memory (CD44hi) and "true naive" (CD44 lo) CD8+ T cells in cells that had undergone the same amount of post-thymic maturation (4 weeks, transgenic mice, different sorts).

2018-06-14 | GSE110030 | GEO

The fate of CD8+ T cells during infection is linked to their developmental origin [Naïve_Timestamp]

Project description:During immune ontogeny the thymus is colonized by distinct waves of hematopoietic stem cells that give rise to unique lineages of immune cells. In this report, we asked whether the developmental origin of CD8+ T cells influences their response to infection later in adulthood. To answer this question, we developed a system to ‘timestamp’ CD8+ T cells in situ at various stages of development (1d and 28d) and examined their behavior at 8 weeks of age. We found that neonatal-derived CD8+ T cells have an intrinsic propensity to become memory phenotype cells prior to infection and are the first cells to proliferate and become effectors after microbial challenge. These data indicate that there are developmental layers in the adult CD8+ T cell response to infection and that the heterogeneity in the effector pool is linked to the variation in the developmental origins of the responding cells. This dataset profiles gene expression in 1day- and 28day-timestamped naïve CD8+ T cells in 8 week old mice.

2018-06-14 | GSE97795 | GEO

Single-cell transcriptional profiling identifies a spectrum of unconventional intraepithelial T lineage cells in human cord blood

Project description:Conventional CD4 and CD8 single positive T cell lineages constitute the main differentiation pathway in the thymus. In human thymus, a minor TCRαβ differentiation pathway diverges from the early double positive stage, consisting of CD10+ PD-1+ cells. These cells are phenotypically and functionally similar to murine agonist-selected intraepithelial T lymphocyte precursors (IELps) which home to the small intestine. Here, the progeny of the human agonist-selected IEL lineage was identified in antigen-inexperienced cord blood (CB) with a polyclonal T cell receptor (TCR) repertoire exhibiting a bias towards early TCR alpha chain rearrangements and elevated autoreactive indices. Single-cell RNA sequencing allowed further delineation of this unconventional lineage in CB. Trajectory analysis, along with TCR repertoire analysis, transcriptomics and proteomics, suggests a precursor-progeny relationship with the thymic IELps. The distinct, heterogeneous CB population can now be defined as CD3+ TCRαβ+ CD4- CCR7- CD26-. Besides recent thymic emigrants, this population also consists of newly identified effector clusters and previously described populations: the suppressive NK receptor expressing CD8+ Treg population, the KIR/NKG2A+ EOMES+ virtual memory population and the CD8αα+ T cell populations. The population shows a discriminating stable HELIOS expression and is exclusively able to downregulate CD8β expression, resulting in double negative T cells. The functional properties of this population suggest that the cells expand on inflammatory cues and exert cytotoxic and proinflammatory activity.

2023-02-10 | PXD033392 | Pride

Gene expression analysis of thymocyte subsets

2011-08-10 | GSE31082 | GEO

Comparison of young and aged mouse CD8 TN, TVM and TMEM cells directly ex vivo and after polyclonal stimulation

Project description:The overall study (Quinn et al. Cell Reports, 2018) aimed to understand why CD8 virtual memory T (TVM) cells become markedly less proliferative in response to TCR-driven signals with increasing age, whereas CD8 true naive (TN) cells maintain their proliferative capacity. Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naïve CD8++ T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Ageing also causes accumulation of antigen-naïve but semi-differentiated “virtual memory” (TVM) cells but their contribution to age-related functional decline is unclear. Here, we show that TVM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naïve T cells (TN cells) retain proliferative capacity in both aged mice and humans. Adoptive transfer experiments in mice illustrated that naïve CD8 T cells can acquire a proliferative defect imposed by the aged environment but age-related proliferative dysfunction could not be rescued by a young environment. Molecular analyses demonstrate that aged TVM cells exhibit a profile consistent with senescence, marking the first description of senescence in an antigenically naïve T cell population.

2018-06-19 | GSE112304 | GEO

RNAseq analysis of mature thymic NKT cells and immature thymic DN1eP cells

Project description:We report the identification of immature thymic CD4(-),CD8(-) double-negative (DN)1e cells with the NKT cell lineage potential. We also analyzed the gene expression profiles of DN1e thymocytes compared with those of mature thymic NKT cell developmental stages termed NKT stage-1, 2, and -3, which are characterized by differential expression levels of NK1.1 and CD44 antigens in C57BL/6 mouse strain. Next generation sequencing of total transcriptomes using total RNA isolated from FACS sorted ex vivo thymic DN1eP (Lin-/CD44+/CD25-/CD24low/CD5+/CD27+/Ly108-/CXCR3+) fraction, and mature thymic alphaGalCer-loaded CD1d dimer+TCRbeta+ NKT cell developmental stage-1 (CD44-/NK1.1-), stage-2 (CD44+/NK1.1-), and stage-3 (CD44+/NK1.1+) cells.

2015-12-31 | E-GEOD-53150 | biostudies-arrayexpress

Expression data from WT and Foxo1 KO CD8+ KLRG1high or KLRG1low populations after LCMV infection

Project description:The forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. We used microarrays to determine whether FOXO1 broadly affects effector and memory differentiation, and to what extent FOXO1 determines the program of memory T cell gene expression. To obtain an unbiased analysis of genes differentially expressed in antigen-specific Foxo1-/- CD8+ T cells responding to infection, we obtained RNA and performed Affymetrix microarray analysis from KLRG1low and KLRG1high FACS-sorted congenically-marked WT and Foxo1-/- P14 cells obtained from mixed transfers, eight days post-infection with LCMV-Armstrong. We carried out gene deletion in Rosa26Cre-ERT2 Foxo1f/f (Foxo1-/-) P14 mice just prior to adoptive transfer (Kerdiles et al., 2009), and transfer equal numbers of P14 cells from the spleens of KO (Foxo1-/- P14) and WT P14 mice. Day8 post infection

2013-04-13 | E-GEOD-46025 | biostudies-arrayexpress

Gene expression analysis of thymocyte subsets

Project description:Mouse thymocytes can be classified into four major subsets based on expression of CD4 and CD8 co-receptors. CD4-CD8- (double negative, DN) cells become CD4+CD8+ (double positive, DP) cells following productive T cell receptor (TCR) beta chain rearrangement. A small proportion of DP cells are selected through interaction of clonal TCRalpha/beta and MHC self peptide complex expressed on thymic stromal cells. DP cell expressing MHC class I-restricted TCR become CD4-CD8+ cells, which will finally differentiate into cytotoxic T cells, while MHC class II restricted selection generates CD4+CD8- helper lineage T cells. We used microarrays to identify genes important for thymocyte differentiation and lineage determination by profiling gene expression in different thymocyte subsets. Mouse thymocytes were divided into four subsets based on CD4, CD8a, and TCRb expression and purified by flw cytometry. FACS purified DN (CD4-CD8a-TCRb-), DP (CD4+CD8a+), CD4SP (CD4+CD8a-TCRbhi) and CD8SP (CD4-CD8a+TCRbhi) populations were lysed in Trizol, and provided to the Genomics Core Facility of the Memorial Sloan-Kettering Cancer Center (MSKCC) for quality control, quantification, reverse transcription, labeling and hybridization to MOE430A 2.0 microarray chips (Affymetrix). Arrays were scanned per the manufacturer’s specifications for the Affymetrix MOE430v2 chip.

2011-08-09 | E-GEOD-31082 | biostudies-arrayexpress

Chronic viral infection of naive, effector, memory and exhausted virus-specific CD8 T cells

Project description:CD8 T cells normally differentiate from resting naïve T cells into function effector and then memory CD8 T cells following acute infections. During chronic viral infections, however, virus-specific CD8 T cells often become exhausted. We used microarrays to examine the gene expression differences between naive, effector, memory and exhausted virus-specific CD8 T cells following lymphocytic choriomeningitis virus infection. Keywords: infection response

2007-11-27 | GSE9650 | GEO

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