Expression level of BTN3A1 on the surface of CD14+ monocytes is a potential predictor of γδ T cell expansion efficiency

2021 ◽  
Author(s):  
Mako Tomogane ◽  
Maho Omura ◽  
Yusuke Sano ◽  
Daiki Shimizu ◽  
Yuki Toda ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Expression Level ◽  
Γδ T Cell ◽  
Potential Predictor ◽  
T Cell Expansion

scholarly journals Costimulation of γδTCR and TLR7/8 promotes Vδ2 T-cell antitumor activity by modulating mTOR pathway and APC function

2021 ◽  
Vol 9 (12) ◽  
pp. e003339
Author(s):  
Huaishan Wang ◽  
Hui Chen ◽  
Shujing Liu ◽  
Jie Zhang ◽  
Hezhe Lu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
Γδ T Cells ◽  
Mtor Pathway ◽  
Two Dimensional ◽  
Γδ T Cell ◽  
T Cell Expansion ◽  
Antigen Presenting

BackgroundGamma delta (γδ) T cells are attractive effector cells for cancer immunotherapy. Vδ2 T cells expanded by zoledronic acid (ZOL) are the most commonly used γδ T cells for adoptive cell therapy. However, adoptive transfer of the expanded Vδ2 T cells has limited clinical efficacy.MethodsWe developed a costimulation method for expansion of Vδ2 T cells in PBMCs by activating γδ T-cell receptor (γδTCR) and Toll-like receptor (TLR) 7/8 using isopentenyl pyrophosphate (IPP) and resiquimod, respectively, and tested the functional markers and antitumoral effects in vitro two-dimensional two-dimensional and three-dimensional spheroid models and in vivo models. Single-cell sequencing dataset analysis and reverse-phase protein array were employed for mechanistic studies.ResultsWe find that Vδ2 T cells expanded by IPP plus resiquimod showed significantly increased cytotoxicity to tumor cells with lower programmed cell death protein 1 (PD-1) expression than Vδ2 T cells expanded by IPP or ZOL. Mechanistically, the costimulation enhanced the activation of the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (PKB/Akt)–the mammalian target of rapamycin (mTOR) pathway and the TLR7/8–MyD88 pathway. Resiquimod stimulated Vδ2 T-cell expansion in both antigen presenting cell dependent and independent manners. In addition, resiquimod decreased the number of adherent inhibitory antigen-presenting cells (APCs) and suppressed the inhibitory function of APCs by decreasing PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in these cells during in vitro Vδ2 T-cell expansion. Finally, we showed that human Vδ2 T cells can be expanded from PBMCs and spleen of humanized NSG mice using IPP plus resiquimod or ZOL, demonstrating that humanized mice are a promising preclinical model for studying human γδ T-cell development and function.ConclusionsVδ2 T cells expanded by IPP and resiquimod demonstrate improved anti-tumor function and have the potential to increase the efficacy of γδ T cell-based therapies.

scholarly journals Neuronal-Activated ILC2s Promote IL-17A Production in Lung γδ T Cells During Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Weiwei Chen ◽  
Dengming Lai ◽  
Yuehua Li ◽  
Xueke Wang ◽  
Yihang Pan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
Cecal Ligation ◽  
Γδ T Cells ◽  
Lymphoid Cells ◽  
Γδ T Cell ◽  
Neuronal Regulation ◽  
T Cell Expansion

BackgroundStudies have revealed important roles for IL-17A in the development of acute lung injury (ALI) following sepsis. However, the mechanism underlying the regulation of lung IL-17A remains to be fully addressed. Recent studies suggested the effect of neuromedin U (NMU) on immune cell activation and the role of group 2 innate lymphoid cells (ILC2s) in the modulation of IL-17A production. We aimed to gain in-depth insight into the mechanism underlying sepsis-induced lung IL-17A production, particularly, the role of NMU in mediating neuronal regulation of ILC2s and IL-17A-producing γδ T cells activation in sepsis.MethodsWild type mice were subjected to cecal ligation and puncture (CLP) to induce sepsis with or without intraperitoneal injection of NMU. The levels of ILC2s, γδ T cells, IL-17A, NMU and NMU receptor 1 (NMUR1) in the lung were then measured. In order to determine the role of NMU signaling in ILC2 activation and the role of ILC2-released IL-9 in ILC2-γδ T cell interaction, ILC2s were sorted, and the genes of nmur1 and il9 in the ILC2s were knocked down using CRISPR/Cas9. The genetically manipulated ILC2s were then co-cultured with lung γδ T cells, and the levels of IL-17A from co-culture systems were measured.ResultsIn septic mice, the levels of NMU, IL-17A, ILC2s, and IL-17A-producing γδ T cells in the lung are significantly increased, and the expression of NMUR1 in ILC2s is increased as well. Exogenous NMU further augments these increases. The main source of IL-17A in response to CLP is γδ T cells, and lung nmur1 is specifically expressed in ILC2s. In vitro co-culture of ILC2s and γδ T cells leads to increased number of γδ T cells and higher production of IL-17A from γδ T cells, and these alterations are further augmented by septic treatment and exogenous NMU. Genetic knockdown of nmur1 or il9 in ILC2s attenuated the upregulation of γδ T cells and IL-17A production.ConclusionIn sepsis, NMU acting through NMUR1 in lung ILC2s initiates the ILC2 activation, which, in turn, promote IL-17A-producing γδ T cell expansion and secretion of IL-17A. ILC2-derived IL-9 plays an important role in mediating γδ T cell expansion and IL-17A production. This study explores a new mechanism underlying neuronal regulation of innate immunity in sepsis.

Robust γδ+ T cell expansion in infants immunized at birth with BCG vaccine

Vaccine ◽  
2007 ◽  
Vol 25 (34) ◽  
pp. 6313-6320 ◽  
Author(s):  
T.N. Mazzola ◽  
M.T.N. Da Silva ◽  
Y.M.F. Moreno ◽  
S.C.B.S. Lima ◽  
E.F. Carniel ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Bcg Vaccine ◽  
Γδ T Cell ◽  
T Cell Expansion

scholarly journals Optimized protocols for γδ T cell expansion and lentiviral transduction

2019 ◽  
Author(s):  
Rui‑Ning Wang ◽  
Qian Wen ◽  
Wen‑Ting He ◽  
Jia‑Hui Yang ◽  
Chao‑Ying Zhou ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Γδ T Cell ◽  
Lentiviral Transduction ◽  
T Cell Expansion

scholarly journals Metformin Promotes the Protection of Mice Infected With Plasmodium yoelii Independently of γδ T Cell Expansion

2018 ◽  
Vol 9 ◽  
Author(s):  
Mana Miyakoda ◽  
Ganchimeg Bayarsaikhan ◽  
Daisuke Kimura ◽  
Masoud Akbari ◽  
Heiichiro Udono ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Plasmodium Yoelii ◽  
Γδ T Cell ◽  
T Cell Expansion

Infliximab Drives Gamma-Delta T Cell Expansion In Crohn's Disease – a Predictor of Lymphoma Risk?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4131-4131
Author(s):  
Jens Kelsen ◽  
Heinrich Schwindt ◽  
Anders Dige ◽  
Francesco d'Amore ◽  
Finn Skou Pedersen ◽  
...  
Keyword(s):  
T Cells ◽  
Crohn’S Disease ◽  
T Cell ◽  
Crohn's Disease ◽  
Cell Expansion ◽  
Γδ T Cells ◽  
Γδ T Cell ◽  
Gamma Delta ◽  
Cell Percentage ◽  
T Cell Expansion

Abstract Abstract 4131 Background: Due to the widespread use of combined immunosuppressive therapy in the management of Crohn's disease (CD), the risk of malignant lymphoproliferation, including the fatal hepato-splenic T cell lymphoma (HSTCL), has become a major concern. We investigated dynamic changes of peripheral gamma-delta (γδ)-T cells during CD treatment with the anti-TNF-α-antibodies infliximab (Remicade®) and adalimumab (Humira®). Methods: Forty-six patients with active CD and nine healthy volunteers were analysed. Patients delivered blood samples before and 1, 7, and 42 days after infliximab 5 mg/kg (20 patients) or adalimumab given as induction with 160 mg and 80 mg after 2 weeks and subsequently 40 mg every other week (26 patients). The γδ-T cells were analysed using FACS analysis. Patients with high percentages of peripheral γδ-T cells were characterized by PCR-assessment of γδ-T cell clonality. Results: Of 46 patients included in the analysis, 35 (76%) had γδ-T cell levels comparable to those of healthy individuals (mean: 1.6%; 95% CI: 1.3–2.0%). Higher γδ-T cell levels from 5% up to 15% occurred in 11 patients (24% of the total cohort). A high γδ-T cell level was associated with non-smoker status and young age. In 18 patients receiving thiopurines or methotrexate, the mean baseline γδ-T cell percentage was 4.4% (95% CI: 2.1–6.7%). In three male CD patients with high baseline values, the γδ-T cell percentage doubled within 24 hours following infliximab therapy. Another male patient on infliximab monotherapy presented with a predominantly clonal baseline γδ-T cell population as high as 20%, further increasing to 25% shortly after infliximab treatment. Conclusion: One fourth of the CD patients treated with immunomodulators had constitutive high levels of circulating γδ-T cells, and infliximab aggravates this γδ-T cell expansion. We raise the hypothesis that such patients may be at increased risk of developing a malignant γδ-T cell lymphoproliferation. Disclosures: No relevant conflicts of interest to declare.

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