PTPMT1 is critical for both expansion and differentiation of activated CD8 T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA894154 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22028430_1.fastq.gz | Fastqsanger.gz | |||
| SRR22028430_2.fastq.gz | Fastqsanger.gz | |||
| SRR22028431_1.fastq.gz | Fastqsanger.gz | |||
| SRR22028431_2.fastq.gz | Fastqsanger.gz | |||
| SRR22028432_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:To understand the function of PTPMT1 in CD8 T cells responses, we characterized the transcriptomes of activated CD8+ T cells from PTPMT1 wildtype and knockout mice
2023-11-21 | GSE216523 | GEO
Project description:TGFb signaling is a major pathway associated with poor clinical outcome in patients with
advanced metastatic cancers and non-response to immune checkpoint blockade, particularly in the immune-excluded tumor phenotype. While previous pre-clinical studies demonstrated that converting tumors from an excluded to an inflamed phenotype and curative anti-tumor immunity require attenuation of both PD-L1 and TGFb signaling, the underlying cellular mechanisms remain unclear. Recent studies suggest that stem cell-like CD8 T cells (TSCL) can differentiate into non-exhausted CD8 T effector cells that drive durable anti-tumor immunity. Here, we show that TGFb and PD-L1 restrain TSCL expansion as well as replacement of progenitor exhausted and dysfunctional CD8 T cells with non-exhausted IFNghi CD8 T effector cells in the tumor microenvironment (TME). Blockade of TGFb and PD-L1 generated IFNghi CD8 T effector cells with enhanced motility, enabling both their accumulation in the TME and increased interaction with other cell types. Ensuing IFNg signaling markedly transformed myeloid, stromal, and tumor niches to yield a broadly immune-supportive ecosystem. Blocking IFNg completely abolished the effect of anti-PD-L1/ TGFb combination therapy. Our data suggest that TGFb works in concert with PD-L1 to prevent TSCL expansion and replacement of exhausted CD8 T cells with fresh CD8
T effector cells, thereby maintaining the CD8 T cell compartment in a dysfunctional state.
2023-06-16 | MSV000092193 | MassIVE
Project description:CD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets. To identify Runx3 regulated genes, CD8+ T cells were isolated from spleen of WT and Runx3-/- mice . Six samples (3 WT and 3 Runx3-/-) of CD8+ T cells were separately obtained from individual mice, TCR activated and cultured for 4 days with IL-2.
2013-11-18 | E-GEOD-50121 | biostudies-arrayexpress
Project description:During the course of infection, T cells are confronted with a multitude of non self epitopes but only respond to a few epitopes and neglect other potentially immunogenic peptides. Restriction of T cell responses to a small number of selected epitopes (immunodominance) is a central feature of immune responses. Immunodominance is considered to be disadvantageous to the host because it allows pathogens to escape by selectively mutating the relevant epitope(s). Using Affymetrix microarrays, we compared the gene expression profile of unprimed CD8 T cells to that of effector CD8 T cells specific for a dominant (H7a) and a nondominant (HY) Ag. Our key finding is that T cells specific for the dominant and nondominant Ags displayed similar gene expression profiles except for a few gene transcripts, such as Gzma, Sell, Il7r and Klrg1, that contribute to the fitness of effector CD8 T cells. The differences between HY- and H7a-specific CD8 T cells were validated by real-time PCR and flow cytometry analyses. We propose that, by leading to selective expansion of the fittest CD8 effector T cells, immunodominance may be beneficial to the host. Inhibition of T cell response to nondominant Ags would ensure that host resources (APCs, cytokines) for which T cells compete are devoted to T cells that have the best effector potential. One implication is that, in general, favouring expansion of the fittest effector T cells may be more important that increasing the diversity of the T cell repertoire. Experiment Overall Design: B10.H7b female mice were primed by i.p. injection of a cell mixture containing 2 x 107 B10 male splenocytes and 2 x 107 B10.H7b male splenocytes. On day 14 after priming, splenocytes were labeled with anti-CD8 Ab as well as H7a- and HY-Tet labeled with different fluorochromes. Then, three populations of splenocytes were purified using a FACS cell sorting: HYTet+ (n=4), H7aTet+ (n=4), and Tet- (n=5) CD8 T cells. RNA of sorted T cells was extracted and linearly amplified, cRNA was prepared, and Affymetrix Mouse Genome 430 2.0 oligonucleotide arrays were used to analyze gene expression.
2008-06-12 | E-GEOD-2924 | biostudies-arrayexpress
Project description:Robust expansion of adoptively transferred T cells is a prerequisite for effective cancer immunotherapy, but how many genes in the genome modulate T cell expansion remains unknown. Here, we performed in vivo and in vitro CRISPR screens to systematically identify genes influencing CD8 T cell expansion. In the mouse genome, ~ 2,600 and ~ 1,500 genes were required for optimal CD8 T cell expansion in vivo and in vitro, respectively. In vivo-specific CD8 T cell essential genes were enriched in metabolic pathways including mitochondrial metabolism. The strongest repressor of CD8 T cell expansion was Roquin, ablation of which drastically boosted T cell proliferation by enhancing cell cycle progression and upregulation of IRF4. Roquin-deficiency or IRF4 overexpression potently enhanced anti-tumor immunity. These data provide a functional catalog of CD8 T cell fitness genes, and suggest targeting Roquin-IRF4 axis is an effective strategy to enhance efficacy of adoptive transfer therapy for cancer.
2021-10-27 | GSE186284 | GEO
Project description:CD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets.
2013-11-18 | GSE50121 | GEO
Project description:Here we report a new way to reverse the tolerant state of adoptively transferred CD8+ T cells against melanoma through ex vivo expansion with the TLR9 agonist CpG. CpG-generated T cells elicited potent immunity without co-administration of high dose IL-2 or vaccination, which are adjuvants classically required to effectively treat solid tumors. CpG-expanded T cells exhibited an IL-2RhighICOShighCD39low phenotype ex vivo and engrafted robustly in vivo. In culture, B cells were the only cell type essential for imprinting T cells with this phenotype and potent tumor immunity. CpG agonists targeting B cells, but not dendritic cells, generated CD8+ T cell products with remarkable antitumor properties. Purified B cells were sufficient to mediate the CpG-associated changes in T cells. These findings reveal a vital role for B cells in the generation of effective antitumor T cells and have immediate implications for profoundly improving immunotherapy for patients.
2022-02-22 | PXD022909 | Pride
Project description:Immune checkpoint blockade (ICB) enhances tumor-reactive T cell responses against cancer, leading to long-term tumor control and survival in a fraction of patients. Given the increasingly recognized complexity of CD8+ T cell differentiation that occurs in response to chronic antigen stimulation, it remains unclear precisely which T cell differentiation states are critical for the response to ICB, as well as the anatomic sites at which ICB-mediated reinvigoration of these T cells occurs. We used paired single-cell RNA and T cell receptor (TCR) sequencing to profile endogenous, tumor-reactive CD8+ T cells isolated from tumors, tumor-draining lymph nodes, and spleens of mice treated with ICB. We identified an intermediate-exhausted population of T cells in the spleen which underwent the greatest expansion in response to ICB and gave rise to the majority of tumor-infiltrating clonotypes. Increasing concentrations of systemic antigen perturbed the differentiation of this phenotype towards an exhausted_KLR state, while a lack of cross-presentation of tumor-derived antigen blunted differentiation in the spleen. We identified an analogous population of exhausted_KLR CD8+ T cells in matched human tumor and blood samples that exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen in coordinating the differentiation and expansion of tumor-infiltrating T cell clonotypes in response to ICB.
2024-07-19 | GSE270050 | GEO
Project description:CD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN-γ and TNF-α. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration. This study identifies a novel, previously undescribed role of CD4+ T cells to prevent immediate dysfunction and features of exhaustion in CD8+ T cells following antigen priming. Splenic AL11-specific CD8 T cells from mice immunized with Ad5HVR48(1-7)-SIV Gag and treated with anti-CD4 antibody or not were purified by FACS on day 14 post-immunization
2016-07-01 | E-GEOD-73001 | biostudies-arrayexpress
Project description:Transcription factors that regulate quiescence, proliferation, and homing of lymphocytes are critical for effective immune system function. In the present study, we demonstrated that the transcription factor ELF4 directly activates the tumor suppressor KLF4 downstream of T cell receptor (TCR) signaling to induce cell cycle arrest in naïve CD8+ T cells. Elf4- and Klf4-deficient mice accumulated CD8+CD44hi T cells during steady-state conditions and generated more memory T cells after immunization. The homeostatic expansion of CD8+CD44hi T cells in Elf4-null mice resulted in a redistribution of cells to non-lymphoid tissue due to reduced expression of the transcription factor KLF2, and the surface proteins CCR7 and CD62L. This work describes the combinatorial role of lymphocyte-intrinsic factors in the control of T cell homeostasis, activation and homing. Experiment Overall Design: CD8 T cells were purified from spleen of wild type and Elf4-/- mice and CD8 T cells were left untreated or activated in vitro by culturing on anti-CD3 coated plates and anti-CD28 in media (RPMI 10% FBS supplemented with 5% T-stim) for 3.5 days. Experiment Overall Design: RNAs isolated from wild type and Elf4 -/- CD8+ T cells were used in Affimetrix oligonucleotide arrays either untreated or after 3.5 days of activation.
2009-03-28 | E-GEOD-15324 | biostudies-arrayexpress