Similar Datasets
Project description:Tissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment. 13 samples were analyzed: 5 replicates of memory OT-I CD8+.CD103- T cells isolated from the spleen of mice on day 20 p.i. with VSV-OVA. 5 replicates of memory OT-I CD8+CD103+ T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA; and 3 replicates of memory OT-I.CD8+ CD103- T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA
2012-08-29 | E-GEOD-39152 | biostudies-arrayexpress
Project description:CD8+ tissue resident memory T cells (TRM) develop from effectors that are recruited into peripheral tissues by infection or inflammation where they persist and provide defense against subsequent challenges. Long-term persistence of epidermal TRM requires autocrine TGFβ that is transactivated by integrins expressed on keratinocytes. In response to inflammation, the availability of TGFβ transactivation is limited. Antigen-experienced TRM that encountered antigen in the epidermis during their development are more fit and outcompete bystander TRM for TGFβ transactivation resulting in their enrichment in the epidermis. Transcriptomic analysis of endogenous epidermal TRM revealed that antigen-experienced TRM were enriched for TRM signature genes while bystander TRM retained the transcriptome of an earlier developmental state. Following antigen recall, antigen-experienced TRM displayed accelerated proliferation kinetics compared with bystanders that was determined by the TCR signal-strength during their differentiation the skin. Finally, antigen experienced TRM expressed TGFβRIII, which increases avidity of the TGFβRI/II receptor complex. Selective ablation of Tgfbr3 from antigen experienced TRM reduced their capacity to persist when TGFβ activation was limited thus rendering them phenotypically like bystander TRM. In sum, antigen-driven TCR signaling in the epidermis during TRM differentiation represents a required final step in ontogeny resulting in a lowered requirement on TGFβ transactivation for persistence and increased proliferation during recall responses that together result in the enhanced fitness of antigen-experience epidermal TRM.
2024-12-10 | GSE283941 | GEO
Project description:Although resident memory T cells (TRMs), which are memory T cells that are retained locally within tissues, have recently been described as antigen-specific frontline defenders against pathogens in barrier and non-barrier epithelial tissues, they have also been noted for perpetuating chronic inflammation. Furthermore, the conditions responsible for TRM differentiation are still poorly understood, and their contributions, if any, to sterile models of chronic kidney disease (CKD) remain a mystery. In this study we identify a substantial population of TRMs in the kidneys of mice with aristolochic acid (AA)-induced CKD. Flow cytometry of injured kidneys showed T cells bearing TRM surface markers and single cell RNA sequencing revealed these cells as expressing well-known TRM transcription factors and receptors responsible for TRM differentiation and maintenance. While kidney TRMs expressed Cd44, a marker of antigen experience and T cell activation, their derivation was surprisingly independent of cognate antigen-T cell receptor interactions, as the kidneys of transgenic OT-1 mice still harbored considerable proportions of TRMs after injury. Our results suggest a non-antigen-specific or antigen-independent mechanism capable of generating TRMs in the kidney and highlight the need to better understand TRMs and their involvement in CKD.
2024-03-01 | GSE246803 | 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:OT-1 T-cells were co-cultured either alone in T-cell media supplemented with IL-2 (50IU/mL IL-2), with OVA loaded macrophages, or with both OVA loaded macrophages and CT2A-TRP2-β2mKO tumor cells. Cells were cultured at a 5:1 T-cell to tumor ratio, and 2:1 T-cell to macrophage ratio. After 24 h of co-culture, CD8 T-cells were FACS sorted, and RNA extracted (RNeasy Mini Kit, Qiagen). RNA was analyzed on an nCounter MAX Analysis System (Nanostring) with the PanCancer Immune profiling panel (Nanostring) according to manufacturer instructions. Expression dat OT-1 T-cells were isolated from OT-1 mice by culturing OT-1 splenocytes in T-cell media supplemented with 50IU/mL IL-2 and 1 μM OVA SIINFEKL peptide (Anaspec) for 48 h. Cells were purified for CD8 T-cells as described above and subsequently cultured in TCM with 50IU/mL IL-2, splitting every 24h for a total of 4 days.
2023-05-22 | GSE220960 | GEO
Project description:The purpose of this study were to test the feasibility of using pMan-antigen therapy to induce humoral tolerance. We used OVA as a model protein along with TCR transgenic OT-I and OT-II to study antigen-specific CD4+ T cell phenotypes and transcriptomic responses using RNA-seq readouts.
2023-11-02 | GSE229893 | GEO
Project description:Here we provide a framework to qualtitatively evaluate the tyrosine phosphorylation-mediated signaling pathways triggered by antigen-independent antibody and antigen-specific OVA peptide-MHC using Jurkat T cells expressing OT-1 T cell receptors. Our data suggest that pTyr-mediated regulatory axis triggered by OVA antigen-specific activation of TCR closely resembled that of antigen-independent stimulation using anti-TCR antibody, albeit OVA could likely induce a relatively stronger signaling effect. While data from this study do not invalidate previous studies of T cell signaling using antibody-based stimulation, our data revealed potential advantages of using peptide-MHC tetramers in studying T cell signaling. Antigen-specific activation of the OT-1 TCR using a panel of peptide-MHC tetramers (OVA, T4 and G4) generated data that correlates well with the corresponding binding affinity of the peptide-MHC, consistent with predicted signaling strength. Importantly, the apparent correlation between signaling strength and peptide-MHC affinity enables us to fine-tune the signaling strength of T cell stimulation in future studies, allowing a more precise control of the experimental parameter instead of a more binary antibody-based activation. Overall, we demonstrate the utility of BOOST to reveal new biological insights in the immune system.
2021-04-27 | PXD024579 | Pride
Project description:In a murine, adoptive transfer model of chronic lymphocytic leukemia we injected OT-I cells followed by infection with mCMV-OVA. On day 7 post-infection, OT-I cells from the spleen were FACS sorted and studied with ATAC sequencing and RNA sequencing. In additition to flow cytometry data demonstrating a skewing towards short-lived effector cells and a lower proportion of memory-precursor cells of OT-I cells from CLL mice compared to WT, we also found effector and memory genes epigenetically and transcriptionally altered.
2023-01-19 | GSE185387 | GEO
Project description:The goal of this study is to analyze differences in gene expression of CD8 T cells that are antigen-educated by lymphatic stromal cells versus traditional antigen-presenting cells. Naive antigen-specific CD8 T cells reactive against the model antigen ovalbumin (OVA) were isolated from spleens of OT-I transgenic mice. They were then co-cultured with OVA-pulsed mature dendritic cells (mDCs) versus lymphatic endothelial cells (LECs) for up to 3d. Each day, OT-I cells were isolated and prepared for RNAseq analysis to determine differences in gene expression as a function of antigen-presenting cell. Naive, LEC-educated, or DC-educated OT-I transcriptomes are provided here. Grant ID - AdG-323053 Agency - European Research Council (ERC) Grant Title - LYMPHIMMUNE - Flow in the tumor microenvironment: Linking mechanobiology with immunology Grant ID - R01CA219304 Agency - US National Institutes of Health (NIH) Grant Title - Paradoxical roles of tumor lymphangiogenesis on tumor immunity and implications for immunotherapy
2017-12-31 | GSE88830 | GEO
Project description:Antigen-specific and bystander epidermal CD8+ resident memory T cells
| PRJNA658649 | ENA