PTPMT1 is critical for both expansion and differentiation of activated CD8 T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE216523 | GEO | 2023/11/21
REPOSITORIES: GEO
Similar Datasets
Project description:PTPMT1 is critical for both expansion and differentiation of activated CD8 T cells
| PRJNA894154 | ENA
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:to compare the transcriptomes of naïve CD4+ and CD8+ T-cells from Gfi1-knockout cells with wildtype cells, spleenocytes from wildtype and Gfi-knockout C57Bl/6 mice were isolated, stained with CD44, CD4 and CD8 antibodies and separated by using a FACS Diva (Becton Dickinson). Total RNAs isolated from 2 mice each (approximately 2xE06 cells) were pooled and subjected to microarray analysis on Affymetrix MOE430A_2.0 arrays Experiment Overall Design: 4 samples, 1 replicate per group
2008-10-17 | E-GEOD-4938 | biostudies-arrayexpress
Project description:to compare the transcriptomes of naïve CD4+ and CD8+ T-cells from Gfi1-knockout cells with wildtype cells, spleenocytes from wildtype and Gfi-knockout C57Bl/6 mice were isolated, stained with CD44, CD4 and CD8 antibodies and separated by using a FACS Diva (Becton Dickinson). Total RNAs isolated from 2 mice each (approximately 2xE06 cells) were pooled and subjected to microarray analysis on Affymetrix MOE430A_2.0 arrays Keywords: knockout mice
2008-07-22 | GSE4938 | GEO
Project description:We report the application of 10x Genomics single-cell sequencing technology for high-throughput profiling of gene regulation difference between wildtype and Dapl1 deficient T cell in tumor microenvironments (TILs). Unsupervised clustering identified 6 clusters of CD8 TILs. We find that Dapl1 was predominantly expressed in a TCF1hi CD8 T cell cluster. The Dapl1 deficiency results in expansion of an effector memory-like CD8 TIL subpopulation and concomitant reduction in a subpopulation of exhausted CD8 TILs highlighting a role for Dapl1 in regulating the intratumoral dynamics of CD8 T cells.
2022-04-13 | GSE175689 | GEO
Project description:Successful anti-viral response requires the sustained activation and expansion of CD8+ T cells for periods that far exceed the time limit of physical T cell interaction with antigen-presenting cells (APCs). The expanding CD8+ T cell pool generates the effector and memory cell populations that provide viral clearance and long-term immunity, respectively. Here, we demonstrate that 3BP2 is recruited in cytoplasmic microclusters and nucleates a signaling complex that facilitates MHC:peptide-independent activation of signaling pathways downstream of the TCR. We show that induction of the adaptor molecule 3BP2 is a sensor of TCR signal strength and is critical for sustaining CD8+ T cell proliferation and regulating effector and memory differentiation.
| S-EPMC6701191 | biostudies-literature
Project description:<p>The efficacy of the adaptive immune response declines dramatically with age, but the cell-intrinsic mechanisms driving the changes characteristic of immune aging in humans remain poorly understood. One hallmark of immune aging is the loss of self-renewing naive cells and the accumulation of differentiated but dysfunctional cells within the CD8 T cell compartment. Using ATAC-seq, we first inferred the transcription factor binding activities that maintain the naive and central and effector memory CD8 T cell states in young adults. Integrating our results with RNA-seq, we determined that BATF, ETS1, Eomes, and Sp1 govern transcription networks associated with specific CD8 T cell subset properties, including activation and proliferative potential. Extending our analysis to aged humans, we found that the differences between memory and naive CD8 T cells were largely preserved across age, but that naive and central memory cells from older individuals exhibited a shift toward a more differentiated pattern of chromatin openness. Additionally, aged naive cells displayed a loss in chromatin openness at gene promoters, a phenomenon that appears to be due largely to a loss in binding by NRF1, leading to a marked drop-off in the ability of the naive cell to initiate transcription of mitochondrial genes. Our findings identify BATF- and NRF1-driven gene regulation as targets for delaying CD8 T cell aging and restoring T cell function.</p>
| phs001187 | dbGaP
Project description:CD8+ T cells play a critical role in the immune response to viral pathogens. Persistent human CMV (HCMV) infection results in a strong increase in the number of virus-specific, quiescent effector-type CD8+ T cells with constitutive cytolytic activity, but the molecular pathways involved in the induction and maintenance of these cells are unknown. We show here that HCMV infection induced acute and lasting changes in the transcriptomes of virus-reactive T cells collected from HCMV-seropositive patients at distinct stages of infection. Enhanced cell cycle and metabolic activity was restricted to the acute phase of the response, but at all stages, HCMV-specific CD8+ T cells expressed the Th1-associated transcription factors T-bet (TBX21) and eomesodermin (EOMES), in parallel with continuous expression of IFNG mRNA and IFN-g–regulated genes. The cytolytic proteins granzyme B and perforin as well as the fractalkine-binding chemokine receptor CX3CR1 were found in virus-reactive cells throughout the response. During HCMV latency, virus-specific CD8+ T cells lacked the typical features of exhausted cells found in other chronic infections. Persistent effector cell traits together with the permanent changes in chemokine receptor usage of virus-specific, nonexhausted, long-lived CD8+ T cells may be crucial to maintain lifelong protection from HCMV reactivation. CD8+ T cells of naive, effector, and memory type were isolated from six latently chronic-infected healthy donors. For RNA isolation and microarray analysis, 3 independent donors and a pool of 3 additional healthy individuals were used. Total RNA of all naive CD8+ T cells was pooled and used as a common reference sample.
2010-09-15 | E-GEOD-24151 | biostudies-arrayexpress
Project description:Antigen-specific effector CD8+ T cells deficient in Blimp-1 (Prdm1) do not acquire maximal effector functions, evade terminal differentiation, and more rapidly acquire some hallmark properties of memory CD8+ T cells. In this study, we compared the gene expression profiles of wildtype and Prdm1-/- LCMV-specific effector CD8+ T cells to better understand the molecular mechanisms underlying this striking phenotype. DNA microarray analysis was performed of DbGP33-41 and DbNP396-404 tetramer-positive effector CD8+ T cells FACS-sorted at day 8 post-LCMV infection from four independent samples of either Blimp-1 conditional knockout mice (CKO; Blimp-1flox/flox x GranzymeB-cre+) or wildtype (WT) littermate controls.
2010-08-19 | E-GEOD-17211 | biostudies-arrayexpress
Project description:HMGB1 has been extensively studied as a DAMP, with secreted cytokine function. However, its regulation on T cells, especially the function in the nucleus, has not been elucidated. Here, we extracted the total protein of CD8 T cells and enriched the proteins bound to HMGB1 through IP experiment. We found several proteins binding with HMGB1, which suggested that nuclear HMGB1 might regulate the function of CD8 T cells by interacting with these proteins. In our study, we focused on the binding of HMGB1 and Eomes, and found that HMGB1 supported the expression of IFN-g in CD8 T cells by directly regulating the activity of the transcription factor Eomes of IFN-g. In conclusion, we determined the role of nuclear HMGB1 in the differentiation of CD8 T cells and proved that it played an important role in the anti-tumor program of CD8 T cells.
2024-03-15 | PXD050639 |