Deconvoluting alloimmunity in time and space through Serial Intravascular Staining: Evidence for rapid donor tissue-resident memory T cell resident memory formation during gastrointestinal GVHD.
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ABSTRACT:
PROVIDER: PRJNA597145 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10753300_1.fastq.gz | Fastqsanger.gz | |||
| SRR10753300_2.fastq.gz | Fastqsanger.gz | |||
| SRR10753301_1.fastq.gz | Fastqsanger.gz | |||
| SRR10753301_2.fastq.gz | Fastqsanger.gz | |||
| SRR10753302_1.fastq.gz | Fastqsanger.gz |
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Project description:Here we have applied Serial Intravascular Staining (‘SIVS’), complemented by single cell transcriptomic analysis, to ascertain the time-, tissue- and donor-dependence of T cell infiltration-mediated immune pathology during aGVHD in a non-human primate (NHP) model. We demonstrate rapid differentiation of donor tissue-infiltrating CD8 T cells in situ into tissue-resident memory T cells (TRM), coincident with destruction of aGVHD target tissues. We also combined SIVS with single cell RNA Sequencing (scRNASeq) to identify the transcriptional programs controlling these actively infiltrating cells.
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Project description:Abstract Intravascular staining (ivs) provides an innovative method for distinguishing tissue-resident lymphocytes from those within the organ’s vasculature, a distinction that is particularly important in highly vascularized organs such as the lung. Cells that stain positive for the infusion antibody (ivs+) have generally been considered lingering blood contaminants; however, recent studies have shown that these cells may not be as transitory as originally thought. Here, we utilized ivs staining to differentiate and isolate T cells from both the lung interstitium (ivs-) and lung vasculature (ivs+) of rhesus macaques (RhM). We then characterized and compared these T cell populations via single-cell RNA sequencing (scRNAseq) and flow cytometry. We found that ivs- T cells exhibit a core gene signature resembling that of tissue-resident memory T cells (Trms), whereas ivs+ T cells represent a distinct population with a unique phenotype and transcriptional profile. Notably, CD8+ T cells were enriched within the lung vasculature (ivs+ subset) and predominantly exhibited an effector phenotype, highlighted by increased cytotoxicity. Moreover, these pulmonary vascular “resident-like” CD8+ T cells (ivs+) demonstrated a gene expression profile enriched in transcripts typically associated with a tissue-resident phenotype, as well as cell adhesion markers and pathways involved in vascular/platelet interactions. In Simian Immunodeficiency Virus (SIV) infected RhMs, pulmonary ivs+ CD8+ T cells displayed enhanced effector responses compared to Trms. Our findings suggest that ivs+ T cells in the pulmonary vasculature represent a unique, “resident-like” population with potent effector functions, highlighting their potential significance in pulmonary immunity.
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