Increased effector γδ T cells with enhanced cytokine production are associated with inflammatory abnormalities in severe hand, foot, and mouth disease

Shen, Yanxi; Pan, Zhaojun; Zhang, Li; Xue, Wei; Peng, Mingli; Hu, Peng; Xu, Hongmei; Chen, Min

doi:10.1016/j.intimp.2018.12.067

Cited by 9 publications

(3 citation statements)

References 33 publications

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“…The JNK/MAPK pathway is involved in triggering the release of cytokines and chemokines from immune cells that are essential for antigen presentation, such as CCL5 and IL-1β [ 30 , 31 ]. As shown in Figure S9A and S9B, in addition to the indicated factors that have been demonstrated to be upregulated in activated γδ T cells [ 32 ], the chemokine CCL5, which mediates T cell homing, was found to be highly expressed in ZOL-stimulated γδ T cells. In addition, CCL5 expression in activated γδ T cells was significantly inhibited by SP600125, indicating the regulatory effect of the JNK pathway on CCL5 generation (Figure S9C).…”

Section: Resultsmentioning

confidence: 94%

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK

Wang

Chen

et al. 2023

Cancer Immunol Immunother

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Human Vγ9Vδ2 T cells have attracted considerable attention as novel alternative antigen-presenting cells (APCs) with the potential to replace dendritic cells in antitumor immunotherapy owing to their high proliferative capacity and low cost. However, the utility of γδ T cells as APCs to induce CD8+ T cell-mediated antitumor immune response, as well as the mechanism by which they perform APC functions, remains unexplored. In this study, we found that activated Vγ9Vδ2 T cells were capable of inducing robust CD8+ T cell responses in osteosarcoma cells. Activated γδ T cells also effectively suppressed osteosarcoma growth by priming CD8+ T cells in xenograft animal models. Mechanistically, we further revealed that activated γδ T cells exhibited increased HSP90 production, which fed back to upregulate MyD88, followed by JNK activation and a subsequent improvement in CCL5 secretion, leading to enhanced CD8+ T cell cross-priming. Thus, our study suggests that Vγ9Vδ2 T cells represent a promising alternative APC for the development of γδ T cell-based tumor immunotherapy.

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Section: Resultsmentioning

confidence: 94%

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK

Wang

Chen

et al. 2023

Cancer Immunol Immunother

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“…The JNK/MAPK pathway is involved in triggering the release of cytokines and chemokines from immune cells that are essential for antigen presentation, such as CCL5 and IL-1β (30,31). As shown in Figure S7A and S7B, in addition to the indicated factors that have been demonstrated to be upregulated in activated γδ T cells (32), the chemokine CCL5, which mediates T cell homing, was found to be highly expressed in ZOL-stimulated γδ T cells. In addition, CCL5 expression in activated γδ T cells was signi cantly inhibited by SP600125, indicating the regulatory effect of the JNK pathway on CCL5 generation (Figure S7C).…”

Section: Ccl5 Promotes the Antigen-presenting Function Of γδ T Cellsmentioning

confidence: 88%

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK

Wang

Chen

et al. 2022

Preprint

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Background Human Vγ9Vδ2 T cells have attracted considerable attention as novel alternative antigen-presenting cells (APCs) with the potential to replace dendritic cells in antitumor immunotherapy owing to their high proliferative capacity and low cost. We seek to evaluate the effect of antigen-presenting γδ T cells (γδ T-APCs) in priming tumor-specific immune responses and clarify the mechanism by which γδ T cells develop antigen-presenting features. Methods The effect of γδ T-APCs in inducing antitumor responses of CD8+ T cells against osteosarcoma cells were tested both in vitro and in vivo. The mechanism by which γδ T cells develop APC features were further explored. Results Human γδ T cells stimulated by zoledronate markedly upregulated APC-related markers and effectively activated CD8+ T cells via cross-presentation of tumor antigen. γδ T-APCs were found to induce robust CD8+ T cell responses against osteosarcoma cells in vitro. In xenograft animal models, γδ T-APCs significantly suppressed osteosarcoma growth by priming CD8+ T cells. Mechanistically, activated γδ T cells produced increased HSP90 and fed back to upregulate MyD88, followed by JNK activation and subsequent improved CCL5 secretion, leading to enhanced CD8+ T cell cross-priming. Conclusions This study demonstrates the effect and mechanism of γδ T-APC-mediated cross-presentation in inducing the antitumor responses of CD8+ T cells. Our data suggest Vγ9Vδ2 T cells represent a promising alternative APC for the development of γδ T cell-based tumor immunotherapy.

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“…The porcine γδ T cells are a subset of T cells that have a TCR complex independent of the αβ T cells. Their various potential functions include protecting against extra- and intra-cellular pathogens, performing tumor surveillance, modulating innate and adaptive immune reactions, performing tissue healing, maintaining epithelial cells, reacting against various viral infections, and regulating the physiological organ functions [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Transcriptomic Comparison between Porcine CD8− and CD8+ Gamma Delta T Cells Revealed Distinct Immune Phenotype

Kim

Lim

Mattoo

et al. 2021

Animals

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We aimed to comprehensively understand the functional mechanisms of immunity, especially of the CD8+/− subsets of gamma delta (γδ) T cells, using an RNA-sequencing analysis. Herein, γδ T cells were obtained from bronchial lymph node tissues of 38-day-old (after weaning 10-day: D10) and 56-day-old (after weaning 28-day: D28) weaned pigs and sorted into CD8+ and CD8− groups. Differentially expressed genes (DEGs) were identified based on the CD8 groups at D10 and D28 time points. We confirmed 1699 DEGs between D10 CD8+ versus D10 CD8− groups and 1784 DEGs between D28 CD8+ versus D28 CD8− groups; 646 upregulated and 561 downregulated DEGs were common. The common upregulated DEGs were enriched in the cytokine–cytokine receptor interaction and T cell receptor (TCR) signaling pathway, and the common downregulated DEGs were enriched in the B cell receptor signaling pathway. Further, chemokine-related genes, interferon gamma, and CD40 ligand were involved in the cytokine–cytokine receptor interaction and TCR signaling pathway, which are associated with inter-regulation in immunity. We expect our results to form the basic data required for understanding the mechanisms of γδ T cells in pigs; however, further studies are required in order to reveal the dynamic changes in γδ T cells under pathogenic infections, such as those by viruses.

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Increased effector γδ T cells with enhanced cytokine production are associated with inflammatory abnormalities in severe hand, foot, and mouth disease

Cited by 9 publications

References 33 publications

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK

Comprehensive Transcriptomic Comparison between Porcine CD8− and CD8+ Gamma Delta T Cells Revealed Distinct Immune Phenotype

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