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CD8 Tissue Resident Memory (TRM) induction

ABSTRACT: We investigated the differentiation pattern induced by MAdCAM co stimulation on α4β7+ CD8+ T cells by analyzing their transcriptional signature.

ORGANISM(S): Homo sapiens

PROVIDER: GSE247100 | GEO | 2023/11/06

REPOSITORIES: GEO

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CD8 Tissue Resident Memory (TRM) induction

Project description:CD8 Tissue Resident Memory (TRM) induction

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Vedolizumab efficacy is associated with decreased intracolonic dendritic cells, not memory T cells [P430]

Project description:Background: Vedolizumab, an antibody blocking integrin α4β7, is a safe and effective therapy for Crohn’s disease and ulcerative colitis. Blocking α4β7 from binding its cognate addressin MAdCAM-1 on intestinal blood vessel endothelial cells prevents T cells from migrating to the gut mucosa in animal models. However, data supporting this mechanism of action in humans is limited. Methods: We conducted a cross-sectional case-control study to evaluate the effect of vedolizumab on intestinal immune cell populations while avoiding the confounding effect resolving inflammation could have on the cellularity of the colonic mucosa in treatment-responsive patients. Colon biopsies from 71 case patients receiving vedolizumab were matched with biopsies from 71 control patients, similar in disease type, medications, anatomic location, and inflammation. Biopsies were analyzed by flow cytometry and full mRNA transcriptome sequencing of sorted T cells. Results: No difference was seen between vedolizumab recipients and controls in the quantity of any antigen-experienced lymphocyte subset, nor the quality of the transcriptome in any experienced T cell subset. Fewer naïve colonic B and T cells were seen in vedolizumab recipients than controls, regardless of response. The only immune population that was significantly reduced exclusively in the colonic mucosa of vedolizumab-responsive patients was CD1c+ (BDCA1+) dendritic cells. In blood, these dendritic cells ubiquitously express more α4β7 per cell than almost any other circulating leukocyte, but rapidly downregulate α4β7 expression upon vedolizumab exposure. Conclusions: The clinical efficacy of vedolizumab thus reveals integrin α4β7-dependent dendritic cell migration to the intestinal mucosa to be central to IBD pathogenesis.

2023-08-01 | GSE234736 | GEO

Vedolizumab efficacy is associated with decreased intracolonic dendritic cells, not memory T cells [P444]

2023-08-01 | GSE234981 | GEO

Resident memory CD8 T cells persist for years in human small intestine

Project description:Resident memory CD8 T cells (Trm) have been shown to provide effective protective responses in the small intestine (SI) in mice. A better understanding of the generation and persistence of SI CD8 Trm cells in humans may have implications for intestinal immune-mediated diseases and vaccine development. Analyzing normal and transplanted human SI we demonstrated that the majority of SI CD8 T cells were bona fide CD8 Trm cells that survived for over 1 year in the graft. Intraepithelial and lamina propria CD8 Trm cells showed a high clonal overlap and a repertoire dominated by expanded clones, conserved both spatially in the intestine and over time. Functionally, lamina propria CD8 Trm cells were potent cytokine-producers, exhibiting a polyfunctional (IFN-γ+ IL-2+ TNF-α+) profile, and efficiently expressed cytotoxic mediators after stimulation. These results suggest that SI CD8 Trm cells could be relevant targets for future oral vaccines and therapeutic strategies for gut disorders.

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Tissue-Resident Macrophages Limit Pulmonary CD8 Resident Memory T Cell Establishment.

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Differential effects of ontamalimab versus vedolizumab on immune cell trafficking in intestinal inflammation and IBD

Project description:The anti-MAdCAM-1 antibody ontamalimab demonstrated efficacy in a phase II trial in UC and results of early terminated phase III trials are pending, but its precise mechanisms of action are still unclear. Thus, we explored the mechanisms of ontamalimab and compared it to the anti-α4β7 antibody vedolizumab.

2023-06-05 | GSE230059 | GEO

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

Single cell 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). 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.

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Epithelial organoid supports resident memory CD8 T cell differentiation.

Project description: Not available

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