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Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?

ABSTRACT: Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?

PROVIDER: PRJNA1201156 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32039500_1.fastq.gz	Fastqsanger.gz
	SRR32039500_2.fastq.gz	Fastqsanger.gz
	SRR32039501_1.fastq.gz	Fastqsanger.gz
	SRR32039501_2.fastq.gz	Fastqsanger.gz
	SRR32039502_1.fastq.gz	Fastqsanger.gz

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Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?

Project description:Staphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus-specific CD4+ T cells are often found in the human population and yet a detailed characterization of their phenotypes and how they might in turn impact vaccine efficacy are thus far unknown. Using an activation induced marker assay to sort for S. aureus-specific CD4+ T cells in an effector function-independent manner, single cell transcriptomic analysis was conducted. Remarkably, S. aureus-specific CD4+ T cells consisted not only of a broader spectrum of conventional T cells than previously described but also of Treg. As compared to polyclonally-activated CD4+ T cells, S. aureus-specific Tcon were enriched for the expression of the Th17-type cytokine genes IL17A, IL22 and IL26, while higher percentages of S. aureus-specific Treg expressed the T Cell Immunoreceptor with Ig and ITIM domains (TIGIT), a pleiotropic immune checkpoint. Notably, the antagonistic anti-TIGIT mAb Tiragolumab increased IL-1b production in response to S. aureus in vitro. Therefore, these results uncover the presence of S. aureus-specific TIGIT+ Treg in the blood of healthy subjects that could blunt responses to vaccination and indicate TIGIT as a potential targetable biomarker to overcome pre-exposure-induced immunosuppression.

2025-02-26 | GSE285086 | GEO

<i>Staphylococcus aureus</i>-specific TIGIT<sup>+</sup> Treg are present in the blood of healthy subjects - a hurdle for vaccination?

Project description:Staphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus-specific CD4+ T cells are often found in the human population and yet a detailed characterization of their phenotypes and how they might in turn impact vaccine efficacy are thus far unknown. Using an activation induced marker assay to sort for S. aureus-specific CD4+ T cells in an effector function-independent manner, single cell transcriptomic analysis was conducted. Remarkably, S. aureus-specific CD4+ T cells consisted not only of a broader spectrum of conventional T cells (Tcon) than previously described but also of regulatory T cells (Treg). As compared to polyclonally-activated CD4+ T cells, S. aureus-specific Tcon were enriched for the expression of the Th17-type cytokine genes IL17A, IL22 and IL26, while higher percentages of S. aureus-specific Treg expressed the T Cell Immunoreceptor with Ig and ITIM domains (TIGIT), a pleiotropic immune checkpoint. Notably, the antagonistic anti-TIGIT mAb Tiragolumab increased IL-1β production in response to S. aureus in vitro. Therefore, these results uncover the presence of S. aureus-specific TIGIT+ Treg in the blood of healthy subjects that could blunt responses to vaccination and indicate TIGIT as a potential targetable biomarker to overcome pre-exposure-induced immunosuppression.

| S-EPMC11840346 | biostudies-literature

TIGIT+ Tregs

Project description:TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses. TIGIT+ and TIGIT- Tregs were sorted from naïve Foxp3-GFP KI mice (pooled spleen and lymph nodes) TIGIT: T cell immunoreceptor with Ig and ITIM domains

2014-12-12 | E-GEOD-56299 | biostudies-arrayexpress

The Co-inhibitory Receptor TIGIT has T cell intrinsic functions

Project description:We compared the gene expression in wild type CD4+ T cells stimulated with agonistic anti-TIGIT 4D4 antibody to that of isotype and TIGIT-deficient (KO) controls.

2011-01-01 | E-MEXP-2847 | biostudies-arrayexpress

TIGIT+ Tregs

2014-12-12 | GSE56299 | GEO

Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells

Project description:Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone. However, there remains little consensus on the mechanism(s) of response with this combination. Here we find that a high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation is associated with a clinical benefit in patients who received the combination treatment. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8+ T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.

2024-03-04 | GSE260816 | GEO

Changes in PBMC gene expression profiles after influenza vaccination in healthy human subjects

Project description:Daily sampling of peripheral blood from human subjects vaccinated for influenza was done immediately before vaccination and for 10 days after vaccination. Temporal patterns of gene expression, determined by RNA-seq, in unfractionated PBMC suggested migration of myeloid/dendritic cell lineage cells one day after vaccination. Five subjects, 11 time points per subject (pre-vaccination and daily for 10 days post-vaccination)

2013-08-07 | E-GEOD-45735 | biostudies-arrayexpress

Changes in PBMC gene expression profiles after influenza vaccination in healthy human subjects

2013-08-07 | GSE45735 | GEO

Effect of Tigit deficiency on CD4 T cell

Project description:To investigate the role of TIGIT in CD4+ T cell differentiation, Total CD4+ T cells were isolated from WT or Tigit -/- mice. Cells were stimulated with anti-CD3/CD28 for 3 d. Cells were then collected and total RNA was extracted.

2025-03-26 | GSE274668 | GEO

TIGIT expression on CD8+ T cells correlates with higher cytotoxic capacity

Project description:Persistent exposure to antigen leads to T cell exhaustion and immunologic dysfunction. We examined the immune exhaustion markers TIGIT and PD-1 in HIV-infected and healthy individuals and the relationship with cytotoxic CD8+ T lymphocyte (CTL) activity. Frequencies of TIGIT but not PD-1 positively correlated with CTL activity in HIV-aviremic and healthy individuals; however, there was no correlation in HIV-viremic individuals. Transcriptome analyses revealed upregulation of genes associated with antiviral immunity in TIGIT+ versus TIGIT-CD8+ T cells. Our data suggest that TIGIT+CD8+ T cells do not necessarily represent a state of immune exhaustion and maintain an intrinsic cytotoxicity in HIV-infected individuals.

2021-03-31 | GSE171172 | GEO

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