Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA926497 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23192783_1.fastq.gz | Fastqsanger.gz | |||
| SRR23192783_2.fastq.gz | Fastqsanger.gz | |||
| SRR23192784_1.fastq.gz | Fastqsanger.gz | |||
| SRR23192784_2.fastq.gz | Fastqsanger.gz | |||
| SRR23192785_1.fastq.gz | Fastqsanger.gz |
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Project description:Tissue resident memory T cells (TRM) maintain immunity in diverse sites as determined in mouse models, while their establishment and role in human tissues has been difficult to assess. Here, we investigated human lung TRM generation, maintenance and function in airway samples obtained longitudinally from HLA-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of TRM signature markers including CD69, CD103, and CD49a, while lung-infiltrating recipient T cells gradually acquire TRM phenotypes over months in vivo. Single cell transcriptome profiling of airway T cells reveals that donor T cells comprise two TRM-like subsets with varying levels of expression of TRM-associated genes while recipient T cells comprised non-TRM and similar TRM-like subpopulations, suggesting de novo TRM generation. Transplant recipients exhibiting higher frequencies of persisting donor TRM experienced fewer adverse clinical events such as primary graft dysfunction and acute cellular rejection compared to recipients with low donor TRM persistence, suggesting that monitoring TRM dynamics could be clinically informative. Together, our results provide novel spatial and temporal insights into how human TRM develop, function, persist, and impact tissue integrity within the complexities of lung transplantation.
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Project description:Molecular characterization of tissue-resident memory T cells cultured with or without donor-matched adult stem cell-derived intestinal organoids. Blood derived immune cells were also isolated and cultivated with autologous intestinal organoids for comparison and characterization. All conditions were derived from 3 human individuals and all samples were sequenced after 24h of in vitro culture. Data provides insights on circulating and tissue-resident immune cell populations, how these differentially interact with the epithelium and how these interactions shape both immune and epithelial cell states.
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Project description:The site of transition between tissue resident memory (TRM) and circulating phenotypes of T cells is unknown. We integrated clonotype, alloreactivity and gene expression profiles of graft-repopulating recipient T cells in the intestinal mucosa at the single cell level after human intestinal transplantation. Host-versus-graft (HvG)-reactive T cells mainly distributed to TRM, Teff/TRM and T follicular helper compartments. RNA velocity analysis demonstrated a trajectory from TRM to effector T (Teff)/TRM clusters in association with rejection. By integrating pre- and post-Tx mixed lymphocyte reaction-determined alloreactive repertoires, we observed that pre-existing HvG-reactive T cells that demonstrated tolerance in the circulation were dominated by TRM profiles in quiescent allografts. Putative de novo HvG-reactive clones showed a transcriptional profile skewed to cytotoxic effectors in rejecting grafts. Inferred protein regulon network analysis revealed upstream regulators that accounted for the effector and tolerant T cell states. We demonstrate Teff/TRM interchangeability for individual T cell clones with known (allo)recognition in human gut, providing novel insight into TRM biology.
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Project description:Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating these two CD8+ populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft and lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103- TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.
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Project description:Tissue-resident memory T (TRM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However transcriptional heterogeneity of human intestinal TRM cells remains undefined. Here, we investigated transcriptional and functional heterogeneity of human TRM cells through study of donor-derived intestinal TRM cells from intestinal transplant recipients. Single-cell transcriptional profiling identified two distinct transcriptional states of CD8+ TRM cells, delineated by ITGAE and ITGB2 expression. We defined a transcriptional signature discriminating these two CD8+ populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft and lymphocytes from healthy gut confirmed the two CD8+ TRM phenotypes. CD103+ CD8+ TRM cells produced IL-2, and demonstrated greater polyfunctional cytokine production, while β2-integrin+ CD69+ CD103- TRM cells had higher granzyme expression. Phenotypic and functional analysis of intestinal CD4+ T cells identified many parallels, including a distinct β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ TRM cells.
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