Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA93873 | ENA |
REPOSITORIES: ENA
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Project description:The two major human gd T cell subsets, Vd1 and Vd2, display differences in tissue tropism and agonist responses, but we have little insight into global differences that may exist at the gene expression level. This is due to the small numbers of these cells that can be obtained from healthy donors, which limit comprehensive, comparative gene expression analyses. We established a culture method that expands Vd1 and Vd2 cells from the same PBL preparation to levels sufficient for sorting and microarray analysis. Although the subsets were expanded identically (anti-TCR mAb, plus IL-15), 392 and 614 genes were identified, which were differentially expressed in the two subsets, from two donors, respectively. Approximately 4,500 genes changed in both subsets following PMA/ionomycin treatment; about 50% of these genes were subset-specific. Both subsets responded to a crude LPS preparation, but only 6% of the responsive genes were the same. The differentially expressed genes were consistent with Vd2 cells being more inflammatory and Vd1 cells having more of a regulatory phenotype. Both subsets expressed transcripts encoding an array of innate and NK cell receptors, supporting the relationship of gd?T cells to the innate immune system. Our results show that circulating Vd1 and Vd2 subsets in humans have considerable, inherent differences in gene expression following treatment with non-TCR agonists, supporting unique functional roles for these cells in vivo.
2007-11-08 | E-GEOD-3720 | biostudies-arrayexpress
Project description:Gene expression analysis comparison of ex vivo isolated GD T cell subpopulations Under non-pathological conditions, human gd T cells represent a small fraction of CD3+ T cells in peripheral blood (1-10%). They constitute a unique subset of T lymphocytes that recognize stress ligands or non-peptide antigens through MHC-independent presentation. Major human gd T cell subsets, Vd1 and Vd2, expand in response to microbial infection or malignancy, but possess distinct tissue localization, antigen recognition, and effector responses. We hypothesized that differences at the gene, phenotypic, and functional level would provide evidence that gd T cell subpopulations belong to distinct lineages. Comparisons between each subset and the identification of the molecular determinants that underpin their differences has been hampered by experimental challenges in obtaining sufficient numbers of purified cells. By utilizing a stringent FACS-based isolation method, we compared highly purified human Vd1 and Vd2 cells in terms of phenotype, gene expression profile, and functional responses. We found distinct genetic and phenotypic signatures that define functional differences in gd T cell populations. Differences in TCR components, repertoire, and responses to calcium-dependent pathways suggest that Vd1 and Vd2 T cells are different lineages. These findings will facilitate further investigation into the ligand specificity and unique role of Vd1 and Vd2 cells in early immune responses.
2023-03-29 | GSE224362 | GEO
Project description:The two major human gd T cell subsets, Vd1 and Vd2, display differences in tissue tropism and agonist responses, but we have little insight into global differences that may exist at the gene expression level. This is due to the small numbers of these cells that can be obtained from healthy donors, which limit comprehensive, comparative gene expression analyses. We established a culture method that expands Vd1 and Vd2 cells from the same PBL preparation to levels sufficient for sorting and microarray analysis. Although the subsets were expanded identically (anti-TCR mAb, plus IL-15), 392 and 614 genes were identified, which were differentially expressed in the two subsets, from two donors, respectively. Approximately 4,500 genes changed in both subsets following PMA/ionomycin treatment; about 50% of these genes were subset-specific. Both subsets responded to a crude LPS preparation, but only 6% of the responsive genes were the same. The differentially expressed genes were consistent with Vd2 cells being more inflammatory and Vd1 cells having more of a regulatory phenotype. Both subsets expressed transcripts encoding an array of innate and NK cell receptors, supporting the relationship of gd?T cells to the innate immune system. Our results show that circulating Vd1 and Vd2 subsets in humans have considerable, inherent differences in gene expression following treatment with non-TCR agonists, supporting unique functional roles for these cells in vivo. Keywords: cell type comparison
2006-02-28 | GSE3720 | GEO
Project description:Gamma-delta (gd) T cells bridge innate and adaptive immunity and have the ability to recognize diverse tumor-associated antigens. However, the function of gd T cells in human gastrointestinal stromal tumor (GIST), the most common type of human sarcoma, is unknown. Here, we combined single-cell RNA-seq (scRNA-seq), immunophenotyping, and next-generation T-cell receptor (TCR) sequencing of sorted human circulating and intratumoral gd T cells to query their impact on tumor immunity in GIST. We identified major subtypes of Vd1 and Vd2 cells, which were more differentiated in tumors. The effector Vd1 subset exhibited higher expression of cytotoxicity-related transcription and exhaustion molecules, and highly expressed the key transcription factors TBX21 and EOMES. Tyrosine kinase inhibitor (TKI) treatment induced the tumor-enriched Vd1 cells to undergo profound phenotype differentiation, alternative clonal expansion, and TCR diversity. Upon antigen exposure, the Vd1 subset maintained enhanced cytotoxicity properties through an innate-effector phenotype and adaptive-like activation. In a genetically engineered murine GIST model, combination therapy of imatinib with a checkpoint inhibitor increased the adaptive immune response of gd T cell subsets in GIST. Collectively, our findings highlight the importance of Vd1-dependent anti-tumor immunity and open the possibility of specific targeting of gd T subsets based on V gene usage for immunotherapy of GIST.
2026-08-07 | GSE300283 | GEO
Project description:Gamma-delta (gd) T cells bridge innate and adaptive immunity and have the ability to recognize diverse tumor-associated antigens. However, the function of gd T cells in human gastrointestinal stromal tumor (GIST), the most common type of human sarcoma, is unknown. Here, we combined single-cell RNA-seq (scRNA-seq), immunophenotyping, and next-generation T-cell receptor (TCR) sequencing of sorted human circulating and intratumoral gd T cells to query their impact on tumor immunity in GIST. We identified major subtypes of Vd1 and Vd2 cells, which were more differentiated in tumors. The effector Vd1 subset exhibited higher expression of cytotoxicity-related transcription and exhaustion molecules, and highly expressed the key transcription factors TBX21 and EOMES. Tyrosine kinase inhibitor (TKI) treatment induced the tumor-enriched Vd1 cells to undergo profound phenotype differentiation, alternative clonal expansion, and TCR diversity. Upon antigen exposure, the Vd1 subset maintained enhanced cytotoxicity properties through an innate-effector phenotype and adaptive-like activation. In a genetically engineered murine GIST model, combination therapy of imatinib with a checkpoint inhibitor increased the adaptive immune response of gd T cell subsets in GIST. Collectively, our findings highlight the importance of Vd1-dependent anti-tumor immunity and open the possibility of specific targeting of gd T subsets based on V gene usage for immunotherapy of GIST.
2026-08-07 | GSE301351 | GEO
Project description:gd T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been documented. Human γδ T cells can be divided into functionally distinct subsets based on T cell receptor Vd usage. Still, the contribution of these different subsets to tumour immunity remains elusive. Here, we provide a detailed gd T cell profiling in colon tumours, comprising mRNA quantification using the Nanostring platform, in combination with mass and flow cytometry and TCR sequencing. δ chain usage in both the macroscopically unaffected colon mucosa and tumours varied considerably between patients, with substantial fractions of Vδ1, Vδ2, and non-Vd1Vd2 cells. Nanostring analyses of flow cytometry sorted Vd1, Vd2 and non-Vd1Vd2 cells showed a large variation in gd T cell subsets between individual tumours, and we suggest that individual gd T cell composition in colon tumours may contribute to the balance between favourable and adverse immune responses, and thereby also patient outcome.
2024-08-01 | GSE266504 | GEO
Project description:Curative strategies for human immunodeficiency virus (HIV-1) infection are hindered by incomplete characterization of the latent reservoir and limited enhancement of anti-HIV immune responses. In this study, we identified a novel dual role for peripheral and tissue-resident Vd1 T cells within the gastrointestinal mucosa of virally suppressed people with HIV. Phenotypic analyses identified an increased frequency of highly differentiated, cytotoxic effector Vd1 T cells that exerted potent inhibition of HIV-1 replication in vitro coinciding with direct increases in cytolytic function. Conversely, we detected an enrichment of HIV-1 DNA in tissue-resident CD4+Vd1 T cells in situ. Despite low CD4 expression, we found circulating Vd1 T cells also contained HIV-1 DNA which was replication-competent. We show that TCR-mediated activation of peripheral Vd1 T cells induced de novo upregulation of CD4 providing a plausible mechanism for increased permissibility to infection. These findings highlight juxtaposing roles for Vd1 T cells in HIV-1 persistence including significant contribution to tissue reservoirs.
2025-01-09 | GSE273603 | GEO
Project description:We performed single-cell RNA sequencing using the BD Rhapsody platform to profile HER2/neu-specific TCR-engineered human T cells following antigen stimulation. TCR-T cells and non-transduced control T cells were analyzed after co-culture with HER2/neu-expressing tumor cells.
2025-12-17 | GSE311201 | GEO
Project description:More than 50% of all patients with colorectal cancer (CRC) develop liver metastasis (CLM) that are characterized by poor prognosis and lack of reliable prognostic markers. Vd1 T cells are gd T innate-like lymphocytes endowed with a broad array of antitumor functions at peripheral tissues, but little is known about their impact in the pathophysiology of CLM. We assessed the phenotype and functions by flow cytometry, clonotype by gdTCR-sequencing, transcriptional profiles by single cell RNA-sequencing and clinical impact of human Vd1 T cells isolated from peripheral blood (PB), tumor-free liver parenchyma surrounding CLM (TFLP) and metastatic tumor (MT) from a large cohort of CLM patients. We show here that CLM tissue is highly enriched of CD69+ Vd1 T effector (TEF) cells in the TFLP area. These cells have a peculiar phenotype, high anti-tumour potential and correlate with a better clinical outcome in terms of lower numbers of liver metastatic lesions and longer overall survival (OS). Moreover, the specific terminally differentiated (TEMRA) CD69+ Vd1 cells can egress CLM tissue to re-circulate in the bloodstream, where they retains high effector functions and show phenotypic/transcriptional and gdTCR profiles that resemble their liver origin. Importantly, high frequencies of CD69+TEMRA Vd1 cells in PB predict a longer OS of CLM patients that is not affected by the neo-adjuvant chemotherapy/immunotherapy regimens administered to CLM patients. The presence at high frequencies of liver memory CD69+TEMRA Vd1 cells in CLM homing to PB represents a new important target to better predict CLM clinical outcomes and to develop novel protocols of adoptive cell transfer therapies.
2023-10-03 | GSE159051 | GEO
Project description:We hypothesised that sustained exposure of naïve CD4+ T cells to IL-6 might imprint them with a distinct transcriptional programme, whose molecular and functional consequences following subsequent TCR ligation was relevant to disease development. Preexposure of healthy naïve CD4+ T-cells to pathophysiological levels of the cytokine caused induction of STAT3 target genes known to discriminate RA patients from disease controls in the clinic. After TCR stimulation IL-6 pre-exposed cells exhibited enhanced proliferative capacity, activation and a propensity towards Th1 differentiation, compared to non-exposed cells.
2019-05-29 | GSE131866 | GEO