The identity of human tissue-emigrant CD8+ T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA680796 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13144700_1.fastq.gz | Fastqsanger.gz | |||
| SRR13144700_2.fastq.gz | Fastqsanger.gz | |||
| SRR13199100_1.fastq.gz | Fastqsanger.gz | |||
| SRR13199100_2.fastq.gz | Fastqsanger.gz | |||
| SRR13199101_1.fastq.gz | Fastqsanger.gz |
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Project description:The identity of human tissue-emigrant CD8+ T cells (scRNAseq, scTCRseq, bulk RNA-seq)
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Project description:CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a regenerative program is not understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted bystander fibroblast and epithelial cell activation, leading to the production of tissue regenerative factors. Tissue remodeling by CD8 T cells could be inhibited by blocking the epidermal growth factor receptor or the effector cytokines IFN-ï§ and TNF. The regenerative program also enhanced tumor spheroid and primary organoid growth. Using single-cell chromatin accessibility and gene expression analysis, we identified a tissue-resident CD8 T cell population in healthy donor skin and adipose tissue with a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. Our findings may help to understand CD8 in the tumor micromilieu and become relevant for the design of CD8 T-cell therapies.
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Project description:Lymphocyte migration is essential for adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies have been restricted to immunological analyses of blood and various tissues. To address this knowledge gap, we used an integrated approach to characterize tissue-emigrant lineages in thoracic duct lymph (TDL). The most prevalent immune cells in human and non-human primate efferent lymph were T cells. Cytolytic CD8+ T cell subsets with effector-like epigenetic and transcriptional signatures were clonotypically skewed and selectively confined to the intravascular circulation, whereas non-cytolytic CD8+ T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Moreover, these anatomically distinct gene expression profiles were recapitulated within individual clonotypes, suggesting parallel differentiation programs independent of the expressed antigen receptor. Our collective dataset provides an atlas of the migratory immune system and defines the nature of tissue-emigrant CD8+ T cells that recirculate via TDL.
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Project description:This SuperSeries is composed of the SubSeries listed below. Abstract Paper: CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a tissue regeneration program is poorly understood. Here, antigen-specific assay systems revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted tissue remodeling. Activated CD8 T cells could produce the epidermal growth factor receptor (EGFR)-ligand amphiregulin (AREG) and sensitize epithelial cells for enhanced regeneration potential. Blocking the EGFR or the effector cytokines IFN-γ and TNF could inhibit tissue remodeling. This regenerative program enhanced tumor spheroid and stem-cell-mediated organoid growth. Using single-cell gene expression analysis, we identified an AREG+, tissue-resident CD8 T-cell population in healthy donor skin and adipose tissue with a strong TCR clonal relation to blood PD1+TIGIT+ CD8 T cells with tissue remodeling abilities. These findings may help to understand the complex CD8 biology in tumors and could become relevant for the design of therapeutic T-cell products.
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Project description:Granzyme K CD8 T cells form a core population in inflamed human tissue
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Project description:Granzyme K CD8 T cells form a core population in inflamed human tissue
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Project description:CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a regenerative program is not completely understood. Here, we have studied antigen-specific assay systems, which revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted bystander fibroblast and epithelial cell activation, leading to the production of tissue regenerative factors such as Amphiregulin (Areg). Tissue remodeling could be inhibited by blocking the epidermal growth factor receptor or the effector cytokines IFN- and TNF. Using single-cell chromatin accessibility and gene expression analysis, we identified a tissue-resident CD8 T cell population in healthy donor skin and adipose tissue with an effector program promoting Areg, TNF and IFNg expression, and a TCR-linkage analysis demonstrated a strong clonal relation between tissue and blood PD1+TIGIT+TOX+ CD8 T cells with tissue remodeling abilities. This regenerative program was also present in anti-cancer associated CD8 populations including chimeric antigen receptor (CAR) CD8 T cells. Once activated, the tissue regenerative program of human CD8 T cells enhanced tumor spheroid, as well as primary liver/bile duct organoid growth. Our findings may help to understand the conflicting CD8 biology in the tumor micromilieu and become relevant for the design of CD8 T-cell therapies for solid tumors.
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Project description:CD8 T lymphocytes are classically viewed as cytotoxic T cells. Whether human CD8 T cells can, in parallel, induce a regenerative program is not completely understood. Here, we have studied antigen-specific assay systems, which revealed that human CD8 T cells not only mediated cytotoxicity, but also promoted bystander fibroblast and epithelial cell activation, leading to the production of tissue regenerative factors such as Amphiregulin (Areg). Tissue remodeling could be inhibited by blocking the epidermal growth factor receptor or the effector cytokines IFN- and TNF. Using single-cell chromatin accessibility and gene expression analysis, we identified a tissue-resident CD8 T cell population in healthy donor skin and adipose tissue with an effector program promoting Areg, TNF and IFNg expression, and a TCR-linkage analysis demonstrated a strong clonal relation between tissue and blood PD1+TIGIT+TOX+ CD8 T cells with tissue remodeling abilities. This regenerative program was also present in anti-cancer associated CD8 populations including chimeric antigen receptor (CAR) CD8 T cells. Once activated, the tissue regenerative program of human CD8 T cells enhanced tumor spheroid, as well as primary liver/bile duct organoid growth. Our findings may help to understand the conflicting CD8 biology in the tumor micromilieu and become relevant for the design of CD8 T-cell therapies for solid tumors.
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