Transcriptomic characterization of human innate T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124731 | GEO | 2019/01/08
REPOSITORIES: GEO
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Project description:Human γδ T cells take a small but important part in the immune system. Human γδ T cells are usually categorized by the V gene of their T cell receptor (TCR) δ chain; most of which are Vδ1+ or Vδ2+. Naive γδ T cells are often found from neonates and cytotoxic γδ T cells (γδCTLs) are frequent in adults. However, phenotypes and the developmental programs of human γδ T cells are not fully clear. Here, by single-cell RNA sequencing (sc-RNAseq) of transcriptome and T cell receptor (sc-TCRseq) on γδ T cells from neonates and adults, we revealed human γδ T cells can be divided as naïve T cells, γδCTLs, and γδNKT cells which are featured by pro-Vδ1, Vδ1, and Vδ2 TCR repertoire, respectively. γδNKT cells can be further described as γδNKT-1, γδNKT-2, and γδNKT-17 cells.
2020-07-31 | GSE149356 | 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:γδ-T lymphocytes are cells of the innate immune system exerting potent natural cytotoxicity against bacteria, viruses and tumours. This ability, coupled with their negligible alloreactivity, makes them attractive for adoptive immunotherapy approaches. To achieve a cell product suitable for clinical use, a protocol offering the possibility to generate and expand high numbers of polyclonal γδ-T cells is required. In this study, we designed a robust protocol to either manually or automatically expand high numbers of functional polyclonal memory γδ-T cells under good manufacturing practice conditions, with the additional possibility of gene-modification to improve anti-tumour activity, proving the feasibility of establishing an allogeneic “third-party T-cell bank” for off-the-shelf use. Engineered artificial antigen-presenting cells (aAPCs) expressing CD86/41BBL/CD40L and the cytomegalovirus (CMV)-antigen-pp65 were used for γδ-T cell production. The presence of CMV-pp65 and CD40L proved to be crucial for expansion of the memory Vδ1 subpopulation. To allow clinical translation and guarantee patient safety, aAPCs were stably transduced with an inducible suicide gene. The proposed cell product represents an attractive therapeutic option endowed with broad clinical applications, including treatment of viral infections in highly immunocompromised patients, treatment of aggressive malignancies refractory to conventional approaches and, ultimately, innovative platform for development of off-the-shelf CAR-T-cell products.
2019-11-18 | PXD015506 | Pride
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:Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but how they contribute to disorders such as SpA is still unclear. Here we describe the presence of particular RORγt+T-betloPLZF- iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt+ iNKT and γδ-hi T cells showed profound IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and γδ-T cells showed a unique Th17 skewed phenotype and gene expression profile. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22+ subsets. Overall, these findings highlight a unique diversity of human RORγt+ T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.
2018-11-17 | GSE122624 | GEO
Project description:This experiment involved isolating monocytes and irradiating them before co-culturing with autologous γδ T-cells at a 1:10 ratio. The cell culture experiments were analysed after HMB-PP activation only, or in combination with different interleukins (IL-2, IL-15, or IL-21). After three days, CD3+ Vδ2+ T-cells were selected via FACs (> 99% purity).
2024-04-01 | E-MTAB-13875 | biostudies-arrayexpress
Project description:Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties pre-programmed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription factor BCL6 is transiently expressed in iNKT cells upon exit from positive selection and is required for their proper development beyond stage 0. Notably, development of MAIT cells is also impaired in Bcl6-deficient mice. We found that BCL6 regulates the expression of genes that are associated with the innate T cell lineage, including PLZF and its targets. BCL6 contributes to a chromatin accessibility landscape that is permissive for the expression of development-related genes and inhibitory for genes associated with naïve T cell programs. Our results reveal novel functions for BCL6 and indicate that this transcription factor controls the inception of innate T cell lineage programming.
2020-07-27 | GSE134210 | GEO
Project description:Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties pre-programmed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription factor BCL6 is transiently expressed in iNKT cells upon exit from positive selection and is required for their proper development beyond stage 0. Notably, development of MAIT cells is also impaired in Bcl6-deficient mice. We found that BCL6 regulates the expression of genes that are associated with the innate T cell lineage, including PLZF and its targets. BCL6 contributes to a chromatin accessibility landscape that is permissive for the expression of development-related genes and inhibitory for genes associated with naïve T cell programs. Our results reveal novel functions for BCL6 and indicate that this transcription factor controls the inception of innate T cell lineage programming.
2021-07-03 | GSE134211 | GEO
Project description:Checkpoint inhibition (CPI), particularly that targeting the inhibitory co-receptor, programmed cell death protein (PD-1), has transformed cancer care. Although CPI can de repress cancer antigen-specific αβ T cells that ordinarily show PD-1-dependent exhaustion, it can also be efficacious against cancers evading αβ T cell recognition. In such settings γδ T cells have been implicated, but the immunological significance of PD-1 expression by tissue associated human Vδ1+ cells remains uncharacterised. Here we demonstrate that a transcriptional signature of intratumoral Vδ1+ cells predicts response to anti-PD-1 in patients with melanomas of relatively low neoantigen load. Moreover, by employing a protocol yielding substantial numbers of human skin γδ cells, we show that PD-1+ Vδ1+ cells display a transcriptomic programme of tissue-residence, survival/self-renewal, and functional competence distinct from the canonical exhaustion programme of co-located PD- 1+ CD8+ αβ T cells. Indeed, skin PD-1+ Vδ1+ cells retained effector responses to T cell receptor signalling that were inhibitable by PD-1 engagement and partially derepressed by CPI. The biological and therapeutic implications are both discussed.
2023-09-25 | GSE232529 | GEO