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Single cell RNA-seq of tumor antigen specific CD8 Tissue Resident Memory (Trm) Cells

ABSTRACT: Purpose: To characterize the tumor-specific TRM cells in LNs, skin, lung and liver in mice with melanoma-associated vitiligo (MAV). scRNAseq was performed to identify populations of CD8 T cells with TRM transcriptional characteristics. Methods: CD8+Thy1.1+ T cells were sorted from DLN, skin lung and liver of MAV mice and scRNA-sequenced Results: Heterogenouse CD8 memory populations with both circulatating and resident phenotypes were identified. Conclusions: Tumor-specific CD8 T cells form TRM responses in tumor-draining LNs.

ORGANISM(S): Mus musculus

PROVIDER: GSE171161 | GEO | 2021/07/04

REPOSITORIES: GEO

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Bulk RNA-seq of tumor antigen specific CD8 Tissue Resident Memory (Trm) Cells

Project description:Purpose: To characterize the tumor-specific TRM cells in LNs, skin, lung and liver in mice with melanoma-associated vitiligo (MAV). Bulk RNA-seq was performed to identify populations of CD8 T cells with TRM transcriptional characteristics. Methods: CD8+THy1.1+ T cells were sorted from DLN, skin lung and liver of MAV mice and bulk RNA-sequenced Results: Heterogenouse CD8 memory populations with both circulatating and resident phenotypes were identified. Conclusions: Tumor-specific CD8 T cells form TRM responses in tumor-draining LNs.

2021-07-04 | GSE169237 | GEO

scRNA/TCR-seq of CD8+CD44+ T cells from tumor draining lymph node and matched vitiligo-affected skin of MAV mice

Project description:Purpose: To identify the presence of endogenous tumor-specific TRM cells in LNs, scRNAseq was performed to identify populations of CD8 T cells with TRM transcriptional characteristics in DLNs. Methods: CD8+CD44+ T cells were sorted from DLN and skin of MAV mice and scRNA-seq in parallel with scTCR-seq was performed. Results: The twenty most expanded clonotypes identified in vitiligo-affected skin of these mice, eight matched to lymph nodes and strikingly, those lymph node clonotypes that had matches in skin mapped almost exclusively to the LN TRM cluster Conclusions: Endogenous tumor-specific CD8 T cells form TRM responses in tumor-draining LNs.

2021-07-04 | GSE169238 | GEO

Dynamic equilibrium of lung Trm dictates waning immunity after IAV infection

Project description:Lung resident memory (Trm) CD8 T cells induced by influenza A virus (IAV), are pivotal for providing heterosubtypic immunity, but are not maintained long term, causing gradual loss of protection. This contrasts sharply with long-term maintenance of Trm induced by localized infections of the skin and other tissues. Here we show that the decline in lung Trm is determined by an imbalance between apoptosis and lung recruitment/conversion to Trm of circulating memory cells. At the cellular level, circulating effector memory (Tem) rather than central memory (Tcm) cells are the precursors for conversion to lung Trm. Time-dependent changes in expression of genes critical for Trm differentiation together with enrichment of Tcm diminish the capacity of circulating memory CD8 T cells to form Trm, explaining why IAV-induced Trm are not stably maintained over time. Importantly, systemic booster immunization, through increasing the number of circulating Tem cells, induces an increase in lung Trm pool, providing a new rational for future IAV vaccines.

2016-11-18 | GSE86973 | GEO

Side population phenotype in quiescent human/murine tissue resident memory (TRM) T cells: Role of ABC transporters and NR4A1 in TRM biology

Project description:The ability to detect and isolate human CD8 TSP (Side population), NaÃ¯ve, Effector memory (EM), Central memory (CM) cells allowed us to compare the global gene expression profiles of these cells. Human TSP cells comprise of distinct gene expression profile specifically enriched for genes overexpressed in TRM cells. RNA samples from CD8 TSP (Side population), NaÃ¯ve, Effector memory (EM), Central memory (CM) cells were amplified, labeled, and hybridized on the Affymetrix Human Genome U133 Plus 2.0 microarray chips. The data were analyzed with GeneSpring GX 12.5 (Agilent Technologies)

2016-08-02 | E-GEOD-85074 | biostudies-arrayexpress

Single cell CITE-seq and VDJ sequencing of CD8+ central memory blood T cells (TCM) and their in-vivo matured tissue-resident memory-like T cells (TRM)

Project description:The aim of the experiment was to understand the clonal relationship between CD8+ central memory blood T cells (TCM) and the in-vivo matured TCM tissue-resident memory-like T cells (TRM) on day 14. TCM were FACS sorted from human PBMCs (n=5). Half of the cells were processed on day 1 and half of the cells of each donor were matured into TRM with anti-CD3, IL-15 and TGF beta for 14 days. Both day 1 TCM and matured day 14 TRM-like cells were further processed using the 5´10X genomics workflow.

2023-06-12 | E-MTAB-12840 | biostudies-arrayexpress

Characterization of resident CD8+ Trm cell populations using whole-genome biomarker analysis

Project description:This study seeks a better understanding of the functional differences between naturally acquired murine CD8+ T resident memory (Trm) cells of three distinct mucosal environments; the small intestine, the lung and the liver. CD8+ Trm cells of healthy young adult mice were retrieved from their respective organ environments by automated organ disintegration and MACS sorting, and compared with each other by whole genome gene expression profiling. Peripheral blood derived circulating CD8+ Tem cells were also analyzed, serving as nonresident peripheral memory T cell controls, in an attempt to identify common characteristics of resident mucosal CD8+ Trm subsets, as well.

2019-01-04 | GSE65044 | GEO

Genome-wide transcriptional analysis of CD8+ brain TRM during CNS autoimmunity

Project description:CD8+ TRM are described in autoimmune and chronic inflammatory diseases. However, we still lack knowledge about mechanisms regulating TRM reactivation, in particular in autoimmune diseases. Here, we investigated in a model of TRM-driven central nervous system autoimmunity the transcriptional landscape of self-reactive brain TRM and the requirement of these cells for CD4+ T cell help.

2023-01-25 | GSE189580 | GEO

Retinoic acid signaling during priming licenses intestinal CD103+ CD8 TRM cell differentiation

Project description:CD8 tissue-resident memory T (TRM) cells provide front-line protection at barrier tissues; however, mechanisms regulating TRM cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.

2023-02-13 | GSE223983 | GEO

RNA-seq transcriptome analysis of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- T cells from healthy human skin

Project description:We report the transcriptome analysis of epidermal CD8 tissue resident memory T (TRM) cells from healthy human skin. Specifically, epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells from healthy human skin were sorted by FACS. Differential gene expression analysis revealed functional dichotomy of epidermal CD8+CD103+CD49a+ and CD8+CD103+CD49- TRM cells.

2017-02-14 | GSE83637 | GEO

Single cell analysis reveals multiple subsets of CD8+ TRM and non-TRM cells with a type 17 signature in the inflamed psoriatic arthritis joint

Project description:CD69+CD103+ tissue-resident memory T-cells (TRM) are increasingly recognised as important drivers of inflammation. To decipher their potential role in inflammatory arthritis, we applied single cell, high-dimensional profiling (CyTOF and scRNAseq) to T-cells isolated from the joint of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identified three broad groups of synovial CD8+ TRM cells: cytotoxic and Treg-like TRM cells were present in the inflamed joints of patients with both PsA and RA, while CD161+CXCR6+ type 17-like TRM cells with a pro-inflammatory cytokine profile (IL-17A+TNFa+IFNg+) and a distinct transcriptomic signature and a polyclonal, but distinct TCR repertoire, were specifically enriched in the inflamed joints of patients with PsA. Type 17-like cells were also enriched in non-TRM CD8+ T-cells in PsA compared to RA. These findings add substantively to the accumulating evidence that the immunopathology of PsA and RA is different, with a particular role for type 17 cells in PsA.

2023-05-17 | GSE216914 | GEO

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