Similar Datasets
Project description:In order to determine transcriptional differences between cells in the draining lymph node and those recently emigrating from the skin, we performed single cell RNA sequencing on KaedeGreen and KaedeRed CD8 T cells 12 days post infection with vaccinia-GP33. CD8+ cells were MACS enriched. Cells were stained with two tetramers (H2-Kb-B8R20-27 and H2-Db-GP33-41) conjugated to APC. Cells were then incubated with TotalSeq anti-APC (Biolegend, 408009)
2024-01-30 | GSE241820 | GEO
Project description:“Stem-like” TCF1+ CD8+ T cells (TSL) are necessary for long-term maintenance of T cell responses and the efficacy of immunotherapy but, as tumors contain signals that should drive T-cell terminal-differentiation, how these cells are maintained in tumors remains unclear. In this study, we found that a small number of TCF1+ tumor-specific CD8+ T cells were present in lung tumors throughout their development. Yet, most intratumoral T cells differentiated as tumors progressed, corresponding with an immunologic shift in the tumor microenvironment (TME) from “hot” (T cell-inflamed) to “cold” (non-T cell-inflamed). By contrast, most tumor-specific CD8+ T cells in tumor-draining lymph nodes (dLNs) had functions and gene expression signatures similar to TSL from chronic LCMV infection, and this population was stable over time, despite the changes in the TME. dLN T cells were the developmental precursors of, and were clonally related to, their more-differentiated intratumoral counterparts. Our data support the hypothesis that dLN T cells are the developmental precursors of the TCF1+ T cells in tumors which are maintained by continuous migration. Finally, CD8+ T cells similar to TSL were also present in LNs from lung adenocarcinoma patients, suggesting a similar model may be relevant in human disease. Thus, we propose that the dLN TSL reservoir has a critical function in sustaining antitumor T cells during tumor development and protecting them from the terminal differentiation that occurs in the TME. Methods: We analyzed single-cell RNA-sequencing to assess the differentiation state and trajectory of the cell subsets present after FACs sorting on endogenous GP33-specific CD8+ T cells from tumors and draining lymph nodes of tumor-bearing KP-NINJA mice, comparing them to GP33-specific CD8+ T cells from spleens of mice infected with acute or chronic LCMV. In order to determine the clonal relationship of these cells from tumors and draining lymph nodes, we analyzed paired single-cell TCR sequencing.
2021-08-27 | GSE182509 | GEO
Project description:There is a paucity of information on dendritic cell (DC) responses to vaccinia virus (VACV), including the traffic of DCs to the draining lymph node (dLN). In this study, using a mouse model of infection, we studied skin DC migration in response to VACV and compared it with the tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG), another live attenuated vaccine administered via the skin. In stark contrast to BCG, skin DCs did not relocate to the dLN in response to VACV. Infection with UV-inactivated VACV or modified VACV Ankara promoted DC movement to the dLN, indicating that interference with skin DC migration requires replication-competent VACV. This suppressive effect of VACV was capable of mitigating responses to a secondary challenge with BCG in the skin, ablating DC migration, reducing BCG transport, and delaying CD4+ T cell priming in the dLN. Expression of inflammatory mediators associated with BCG-triggered DC migration were absent from virus-injected skin, suggesting that other pathways invoke DC movement in response to replication-deficient VACV. Despite adamant suppression of DC migration, VACV was still detected early in the dLN and primed Ag-specific CD4+ T cells. In summary, VACV blocks skin DC mobilization from the site of infection while retaining the ability to access the dLN to prime CD4+ T cells.
| S-EPMC7116689 | biostudies-literature
Project description:There is a paucity of information on dendritic cell (DC) responses to vaccinia virus (VACV), including the traffic of DCs to the draining lymph node (dLN). In this study, using a mouse model of infection, we studied skin DC migration in response to VACV and compared it with the tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guérin (BCG), another live attenuated vaccine administered via the skin. In stark contrast to BCG, skin DCs did not relocate to the dLN in response to VACV. Infection with UV-inactivated VACV or modified VACV Ankara promoted DC movement to the dLN, indicating that interference with skin DC migration requires replication-competent VACV. This suppressive effect of VACV was capable of mitigating responses to a secondary challenge with BCG in the skin, ablating DC migration, reducing BCG transport, and delaying CD4+ T cell priming in the dLN. Expression of inflammatory mediators associated with BCG-triggered DC migration were absent from virus-injected skin, suggesting that other pathways invoke DC movement in response to replication-deficient VACV. Despite adamant suppression of DC migration, VACV was still detected early in the dLN and primed Ag-specific CD4+ T cells. In summary, VACV blocks skin DC mobilization from the site of infection while retaining the ability to access the dLN to prime CD4+ T cells.
| S-EPMC7851745 | biostudies-literature
Project description:Psychrobacter sp. GP33 Genome sequencing and assembly
| PRJNA648467 | ENA
Project description:WT and KO OT1 T cells were isolated from vaccinia-OVA infected ears 21 days post infection
2023-08-08 | GSE223727 | GEO
Project description:Altered CD8 T cell differentiation and functional exhaustion prevent control of chronic virus infection and cancer. Yet, how fate commitment and exhaustion are determined and dynamically modulated throughout persistent infection are unclear. We compared the activation and differentiation of LCMV GP33-specific CD8 TCR transgenic cells (P14) primed at the onset versus in the midst of established persistent LCMV-Clone 13 viral infection. LCMV GP33-specific CD8 TCR transgenic (P14) cells were injected into naïve mice immediately infected with LCMV-Cl13 (Early priming) or into mice that had been infected 21 days earlier with LCMV-Cl13 (Late Priming). Sixty hours post-priming P14 cells were sorted from mice and subjected to RNA seq. We show early primed cells very rapidly exhibit a transcriptional profile of robust activation, effector differentiation and dysfunction, while late primed cells have increased expression of genes involved in memory differentiation and maintenance.
2018-10-09 | GSE105044 | GEO
Project description:We report the transcriptional profiles of human lung and lung draining lymph node T cell subsets that were sorted from paired samples. Naïve, central memory, effector memory and tissue resident memory CD4 and CD8 T cell subsets were sorted by FACS. Samples then underwent RNA sequencing to compare the similarities and differences between these T cell subsets and across tissues.
2019-09-27 | GSE137967 | GEO