Expansion of memory Vδ2 T cells following SARS-CoV-2 vaccination revealed by temporal single-cell transcriptomics
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1083421 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28216700.fastq.gz | Fastqsanger.gz | |||
| SRR28216701.fastq.gz | Fastqsanger.gz | |||
| SRR28216602.fastq.gz | Fastqsanger.gz | |||
| SRR28216702.fastq.gz | Fastqsanger.gz | |||
| SRR28216603.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 184 |
Similar Datasets
Project description:γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection.
2024-03-04 | GSE260763 | GEO
Project description:γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection.
| S-EPMC10954735 | biostudies-literature
Project description:Vγ9Vδ2 T cells are an attractive cell platform for the off-the-shelf cancer immunotherapy due to their lack of alloreactivity and inherent multi-pronged cytotoxicity, which could be further amplified with chimeric antigen receptors (CARs). In this study, we sought to enhance the in vivo longevity of CAR-Vδ2 T cells by modulating ex vivo manufacturing conditions and selecting an optimal CAR costimulatory domain. Specifically, we compared the anti-tumor activity of Vδ2 T cells expressing anti-CD19 CARs with costimulatory endodomains derived from CD28, 4-1BB or CD27 and generated in either standard fetal bovine serum (FBS)- or human platelet lysate (HPL)-supplemented medium. We found that HPL supported greater expansion of CAR-Vδ2 T cells with comparable in vitro cytotoxicity and cytokine secretion to FBS-expanded CAR-Vδ2 T cells. HPL-expanded CAR-Vδ2 T cells showed enhanced in vivo anti-tumor activity with longer T cell persistence compared to FBS counterparts, with 4-1BB costimulated CAR showing the greatest activity. Mechanistically, HPL-expanded CAR Vδ2 T cells exhibited reduced apoptosis and senescence transcriptional pathways compared to FBS-expanded CAR-Vδ2 T cells and increased telomerase activity. This study supports enhancement of therapeutic potency of CAR-Vδ2 T cells through a manufacturing improvement.
2024-08-16 | GSE247760 | GEO
Project description:Gamma delta (γδ) T cells reside within human tissues including tumors, but their role in mediating anti-tumor response with immune checkpoint inhibition is unknown. Using single-cell approaches, we found that kidney cancers are infiltrated by diverse Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted alpha beta (ab) CD8+ T cells as well as canonical markers of terminal T cell exhaustion including PD-1, TIGIT and TIM-3. While Vδ2- γδ T cells have blunted IL-2 production, they retain expression of cytolytic effector molecules and costimulatory receptors like 4-1BB. Exhausted Vδ2- γδ T cells are comprised of three distinct populations that lack TCF-7, are clonally expanded, express of cytotoxic molecules, and possess multiple Vδ2- TCRs. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pre-treatment tumor biopsies predicted subsequent clinical responses to PD-1 blockade in vivo in cancer patients. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to anti-tumor efficacy.
2023-01-31 | GSE223808 | GEO
Project description:Gamma delta (γδ) T cells reside within human tissues including tumors, but their role in mediating anti-tumor response with immune checkpoint inhibition is unknown. Using single-cell approaches, we found that kidney cancers are infiltrated by diverse Vδ2- γδ T cells, with equivalent representation of Vδ1+ and Vδ1- cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2- T cells can express the transcriptional program of exhausted alpha beta (ab) CD8+ T cells as well as canonical markers of terminal T cell exhaustion including PD-1, TIGIT and TIM-3. While Vδ2- γδ T cells have blunted IL-2 production, they retain expression of cytolytic effector molecules and costimulatory receptors like 4-1BB. Exhausted Vδ2- γδ T cells are comprised of three distinct populations that lack TCF-7, are clonally expanded, express of cytotoxic molecules, and possess multiple Vδ2- TCRs. Human tumor-derived Vδ2- γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2- T cells in pre-treatment tumor biopsies predicted subsequent clinical responses to PD-1 blockade in vivo in cancer patients. Thus, Vδ2- γδ T cells within the tumor microenvironment can contribute to anti-tumor efficacy.
2023-01-31 | GSE223806 | GEO
Project description:We utilized RNA-seq to identify differential gene expression in Vγ9 Vδ2 gdT cells isolated from human PBMCs upon TCR stimulation. We find that ~30% genes are commonly up- and down-regulated between different phosphoantigen treatments (p<0.05). Inhibition of Notch signaling alongside TCR activation results in downregulation of many effector genes in Vγ9 Vδ2 T cells.
2021-08-25 | GSE168642 | GEO
Project description:Allogeneic Vγ9Vδ2 (Vδ2) T cells are attractive candidates in the development of cancer therapies due to their demonstrated safety in allogeneic settings and innate ability to fight tumors. However, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor evasion. To address these limitations, we have generated Vδ2 T cells with improved properties. By utilizing CD16 as a donor selection biomarker, we have generated Vδ2 T cells with high levels of cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) function, and RNA sequencing characterization supports the increased effector function of Vδ2 T cells obtained from CD16 high (CD16Hi) donors. Further improvement was achieved through CAR and IL-15 engineering techniques. Preclinical studies in two ovarian cancer models showed that engineered CD16Hi Vδ2 T cells are both effective and safe, targeting tumors through multiple mechanisms, exhibiting long-term persistence in vivo, and not causing graft-versus-host disease. These findings support the potential of engineered CD16Hi Vδ2 T cells as a viable cancer therapy option.
2023-06-29 | GSE235755 | GEO
Project description:The effectiveness of the seasonal influenza vaccine varies between individuals. Specific risk groups with comorbidities, such as the obese, have an increased risk of infection even when vaccinated. It has been proposed that a heightened baseline inflammatory state and alterations in adaptive immune cell populations in obese individuals may adversely impact immune response to pathogens and vaccines. Therefore, understanding differences in vaccine response in obese individuals is critical for the development of improved influenza vaccine design and strategies. Previously, we identified a transcriptomic signature prior to seasonal influenza vaccination that is predictive of an individual’s response to the influenza vaccine. To understand the dynamics of the host response following vaccination we studied systemic gene expression from whole blood collected from 163 vaccinated individuals on days 3, 7, and 28 post-vaccination. Gene expression profiles were compared between high and low vaccine responders in both obese and non-obese groups. We detected characteristic changes in gene expression over time, with a peak at day 7 post-vaccination. A large subset of genes associated with the adaptive immune response exhibited significantly different expression in high- and non- vaccine responders. Distinct gene sets presented differing temporal patterns in different weight and response groups, indicative of molecular processes impacting the immune response to vaccination.
2025-06-25 | GSE271520 | GEO
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
Project description:B cells play a central role in the immune response to both SARS-CoV-2 infection and vaccination, but the development of the B cell receptor (BCR) repertoire in both contexts has not been defined nor compared. We analysed serial samples from 171 SARS-CoV-2-infected individuals with a range of disease severities together with 63 vaccine recipients, and found marked differences in the global BCR repertoire after natural infection compared to vaccination. Following infection, the proportion of BCRs bearing IgG1/3 and IgA1 isotypes increased, somatic hypermutation (SHM) was markedly decreased and, in patients with severe disease, expansion of IgM and IgA clones was observed. In contrast, after vaccination the proportion of BCRs bearing IgD/M isotypes increased, SHM was unchanged and expansion of IgG clones was prominent. Infection generated a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein whilst vaccination produced a more focused response mainly targeting the spike’s receptor-binding domain. These findings offer insights into how different immune exposure to SARS-CoV-2 impacts upon BCR repertoire development, potentially informing vaccine strategies.
| EGAS00001005816 | EGA