Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA396946 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To understand the impact of TCR affinity during priming on memory formation, we performed transcriptional profiling of OT-1 cells at different time points after stimulation with high- or low-affinity ligands. Our findings indicate that low-affinity stimulaation is associated with earlier memory formation.
2020-01-06 | GSE102189 | GEO
Project description:Resident memory T (TRM) cells in the lung are vital for heterologous protection against influenza A virus (IAV). Environmental factors are necessary to establish lung TRM, however the role of T cell intrinsic factors like T cell receptor (TCR) signal strength have not been elucidated. Here we investigated the impact of TCR signal strength on the generation and maintenance of lung TRM cells after IAV infection. We inserted high and low affinity OT-I epitopes into IAV and infected mice after transfer of OT-I T cells. We uncovered a bias in TRM formation in the lung elicited by lower affinity TCR stimulation. TCR affinity did not impact the overall phenotype or long-term maintenance of lung TRM cells. Overall, these findings demonstrate that TRM formation is negatively correlated with increased TCR signal strength. Lower affinity cells may have an advantage in forming TRM to ensure diversity in the antigen-specific repertoire in tissues.
2019-06-18 | GSE130609 | GEO
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
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 | GSE152392 | GEO
Project description:We compared the transcriptional profile of FACS-purified total effector, KLRG1+ effector and KLRG1- effector Lck-Cre;Ptpn2fl/fl and Ptpn2fl/fl OT-I cells from spleens of acutely infected mice. As expected, we found a large number of differentially expressed genes (DEG; |log2(fold-change)| >1; false discovery rate <0.05) between KLRG1– and KLRG1+ subsets of both Lck-Cre;Ptpn2fl/fl (712 DEG) and Ptpn2fl/fl (528 DEG) OT-I cells. Furthermore, we found 190 DEGs between total populations of Ptpn2-deficient and control OT-I cells. Considerably fewer genes were differentially expressed between Lck-Cre;Ptpn2fl/fl and Ptpn2fl/fl OT-I cells amongst the KLRG1– (93 DEG) and KLRG1+ (59 DEG) subsets. Hierarchical clustering analysis further revealed clustering of KLRG1– cells of both genotypes with total Ptpn2fl/fl OT-I cells, whereas KLRG1+ cells of both genotypes clustered with total Lck-Cre;Ptpn2fl/fl OT-I cells. Gene set enrichment analysis further showed that differential gene profiles between Lck-Cre;Ptpn2fl/fl and Ptpn2fl/fl OT-I cells for all subfractions (total, KLRG1+, KLRG1–) were enriched significantly for previously identified effector versus memory CD8+ T cell signature genes. Taken together, these findings indicate that after in vivo priming following HSV infection, Ptpn2 deficiency resulted in the preferential generation of OT-I cells with a transcriptional profile biased towards more terminally differentiated KLRG1+ effector cells with restricted memory potential.
2021-02-04 | GSE166133 | GEO
Project description:The memory CD8 T cell pool must select for high-affinity clones to efficiently counter re-infection yet must retain a level of clonal diversity to allow recognition of pathogens with mutated immuno-dominant epitopes. How this is mediated is unclear, especially in the context of a selective drive for antigen-affinity. We find that low-affinity memory exclusively depends on the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the pro-survival protein Bcl-2. At higher signal intensity T-bet is induced which suppresses Bcl-2, generating a survival advantage for low-affinity cells. High-affinity cells form memory independent of Eomes and have a proliferative advantage over low-affinity cells, which compensates for their survival deficit. Thus, we demonstrate on a molecular level how sufficient diversity of the memory pool is established in an environment of affinity-based selection.
2020-08-01 | GSE118174 | GEO
Project description:Asymmetric cell division (ACD) and the strength of initial T cell receptor (TCR) signaling are both implied to contribute to the establishment of cellular heterogeneity and CD8 T cell effector and memory differentiation. However, on a single cell level it remained unclear whether ACD generates progeny of different fates and whether the strength of TCR signaling affects this mechanism. Therefore, we developed experimental systems allowing monitoring the fate of single daughter cell progenies derived from an ACD either induced by weak or strong TCR stimulation by in vitro live imaging. We used the combinatorial expression of TCF1 and CD62L as markers indicating fate specification a few days after activation and analyzed the transcriptional profiles of in vitro generated CD62L+TCF1+ and CD62L-TCF1- cells derived from either antibody-induced (AB) activation or from gp33 (high affinity) or C6 (low affinity) peptide stimulation and compared them to in vivo generated effector and memory cells, respectively. Therefore, we sorted CD62L+TCF1+ and CD62L-TCF1- cells on day 6 post activation, followed by bulk RNA sequencing and found that CD62L+TCF1+ cells transcriptionally resembled in vivo generated memory cells, whereas CD62L-TCF1- cells were similar to in vivo generated effector cells.
2023-02-17 | E-MTAB-12563 | biostudies-arrayexpress
Project description:Low affinity CTCF binding drives transcriptional regulation whereas high affinity binding encompasses architectural functions.
| PRJNA856492 | ENA
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 vesicular stomatitis virus. 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 70 days post infection with ovalbumin-expressing vesicular stomatitis virus (VSV-OVA) (experiment 3). 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 | GSE110706 | GEO
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