Transcriptomes of Effector Memory T cells undergoing lymphopenia induced proliferation
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ABSTRACT:
PROVIDER: PRJNA633810 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11811458_1.fastq.gz | Fastqsanger.gz | |||
| SRR11811458_2.fastq.gz | Fastqsanger.gz | |||
| SRR11811459_1.fastq.gz | Fastqsanger.gz | |||
| SRR11811459_2.fastq.gz | Fastqsanger.gz | |||
| SRR11811460_1.fastq.gz | Fastqsanger.gz |
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Project description:Transcriptomes of Effector Memory T cells undergoing lymphopenia induced proliferation
| PRJNA633810 | ENA
Project description:Purpose: T cells undergo intense proliferation in the setting of lymphopenia and chemotherapy pre-conditioning is therefore an essential component of CAR-T therapy. Lymphopenia-induced proliferation (LIP) is thought to be mediated primarily by homeostatic cytokines such as IL-7 and IL-15 but little is known regarding the underlying mechanisms in human subjects Methods: We undertook transcriptional analysis of CD4+ and CD8+ T cells following myeloablative autograft stem cell transplantation. Results: T cells at day 12 after transplant were undergoing intense proliferation and the proportion of naïve T cells was markedly reduced and replaced by an effector pool.The proportion of FoxP3+ regulatory cells was almost doubled by day 12 and the global effector T cell pool also displayed a transcriptional profile typical of activated regulatory cells. Transcriptional analysis further revealed intense cell cycle activation driven by fatty acid metabolism and strong signalling responses to interferon. In contrast, TGF- signalling, a major negative regulator of T cell proliferation, was strongly suppressed Conclusions: The human LIP response is thus characterised by intense cytokine and TCR-driven proliferation which drives global T cell activation but also preferentially triggers a regulatory cell expansion which may limit induction of tumour-specific immunity. These features indicate a range of potential therapeutic opportunities to manipulate immunotherapy regimens that incorporate LIP conditioning protocols.
2021-03-03 | GSE150834 | GEO
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.
2005-01-01 | E-TABM-40 | biostudies-arrayexpress
Project description:Expression profiles of in vitro generated CD8+ central memory (CM) and effector/effector memory (E/EM) T cells on Affymetrix GeneChip Murine Genome U74 Version 2 Set MG-U74A, MG-U74B, and MG-U74C. T cells were generated from female P14 T cell receptor transgenic mice on the C57Bl/6 genetic background.
2007-12-15 | E-GEOD-561 | biostudies-arrayexpress
Project description:The goal of this study is to determine if central memory (Tcm) and effector memory (Tem) CD8 T cells can be reprogrammed to change their fate. We demonstrate that genetic ablation of Tle3 can promote generation of Tcm cells at the expense of Tem cells, and this can occur during the effector phase of the immune response.
2023-10-10 | GSE241532 | GEO
Project description:During a T cell response, naïve CD8 T cells differentiate into effector cells. Subsequently, a subset of effector cells termed memory precursor effector cells (MPECs) further differentiates into functionally mature memory CD8 T cells. The transcriptional network underlying this carefully scripted process is not well understood. Here, we report that the transcription factor FoxO1 plays an integral role in facilitating effector to memory transition and functional maturation of memory CD4 and CD8 T cells. We find that FoxO1 is not required for differentiation of effector cells, but in the absence of FoxO1, memory CD8 T cells displayed features of scenescence and progressive attrition in polyfunctionality, which in turn led to impared recall responses and poor protective immunity. These data suggest that FoxO1 is essential for active maintenance of functional CD8 T cell memory and protective immunity. Under competing conditions in bone marrow Single-cell suspensions from splenocytes of eight samples WT (control) and FoxO1-/- (experimental) LCMV-immune mice were prepared using standard procedures. CD8 T cells were then isoloated using Thy1.2 (CD90.2) (30-H12) microbeads (Miltenyi Biotec). Cells were then stained with anti-CD8, anti-CD44 and Db/NP396 MHC class I tetramer. Activated (CD8+CD44hi), naive (CD8+CD44lo), and virus-specific CD8 T cells were sorted using FACSAria II instrument (BD Biosciences). The purity of the cells was >95%. Total RNA was extracted from the sorted cells by Trizol Reagent. RNA samples were reverse transcribed and Cy3-labeled cDNAs were hyrbidized to Agilent whole Mouse Genome Oligo Microarrays. Fluorscence signals were detected using Agilent's Microarray Scanner system, data was analyzed using the Rosetta Resolver gene expression data analysis system and genes with a fold change < and p-values <0.01 were identified. Microarray data discussed in the paper is focused on virus-specific memory CD8 T cells from samples WT_Tet_2 vs KO_Tet_2.
2013-06-25 | E-GEOD-45673 | biostudies-arrayexpress
Project description:Using killer cell lectin-like receptor G1 as a marker to distinguish terminal effector cells from memory precursors, we found that despite their diverse cell fates both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making IL-2 thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid re-call responses. Mechanistic studies showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation towards the tail-end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation Experiment Overall Design: An important question in memory development is understanding the differences between effector CD8 T cells that die versus effector cells that survive and give rise to memory cells. In this study we provide a comprehensive phenotypic, functional and genomic profiling of terminal effectors and memory precursors, towards better understanding the generation of these subsets. The two effector subsets were FACS purified during the early expansion phase (Days 4-5 post-infection) and extensively analyzed for their phenotypic (eg. CD127, CD62L, CD27, Bcl-2, Granzyme B, etc.) and functional properties (cytokine production, cytotoxicity, homeostatic proliferation, recall proliferation), and gene expression profiles (by genome-wide microarray analyses). Mechanistic studies involving the extent of proliferation and duration of antigen stimulation on memory differentiation potential of effectors were also performed using adoptive transfer techniques.
2008-06-11 | E-GEOD-10239 | biostudies-arrayexpress
Project description:Maintenance of memory CD8 T cell effector function is coupled to stability ofeffector DNA methylation programs during homeostatic proliferation
2017-08-03 | GSE98837 | GEO
Project description:Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of naïve or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from naïve or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of naïve cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their naïve or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy. Experiment Overall Design: Effector cells were generated from naive or central memory CD8+ T cells. The cells were then rested (unstimulated) or restimulated (stimulated). This experimental design resulted in 4 groups (Naïve-derived/stimulated, Naïve-derived/unstimulated, Central memory-derived/stimulated, Central memory-derived/unstimulated). Three replicates from independent experiments were analyzed.
2009-06-23 | E-GEOD-16522 | biostudies-arrayexpress
Project description:Differentiation of CD8+ T lymphocytes into effector and memory cells is key for an adequate immune response and relies on complex interplay of pathways that convey signals from cell surface to nucleus. In this study, we fractionated four CD8+ T cell subtypes; naïve, recently activated effector, effector and memory cells into membrane, cytosol, soluble nucleus, chromatin-bound and cytoskeleton compartments. Using LC-MS/MS analysis, identified peptides were matched to human peptides/proteins (SwissProt). Compartment fractionation and gel-LC-MS separation identified 2399 proteins in total. Among these 735 were detected in all five, 241 in four, 257 in three, 368 in two and 798 found in only one fraction. Comparison between the two most different subsets, naïve and effector, yielded 146 significantly regulated proteins.
2016-02-29 | MSV000079540 | MassIVE