scholarly journals PD-1 signaling modulates interferon-γ production by Gamma Delta (γδ) T-Cells in response to leukemia

2018 ◽  
Vol 8 (3) ◽  
pp. 1550618 ◽  
Author(s):  
Timm Hoeres ◽  
Elisabeth Holzmann ◽  
Manfred Smetak ◽  
Josef Birkmann ◽  
Martin Wilhelm
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Interferon Γ ◽  
Gamma Delta

scholarly journals Importance of murine Vδ1+γδ T cells expressing interferon-γ and interleukin-17A in innate protection againstListeria monocytogenesinfection

Immunology ◽  
2008 ◽  
Vol 125 (2) ◽  
pp. 170-177 ◽  
Author(s):  
Satoru Hamada ◽  
Masayuki Umemura ◽  
Takeru Shiono ◽  
Hiromitsu Hara ◽  
Kenji Kishihara ◽  
...  
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Interferon Γ ◽  
Interleukin 17A

scholarly journals Alterations in Gamma-Delta T Cells in Patients With Primary Biliary Cholangitis

2021 ◽  
Author(s):  
Sha Chen ◽  
Tingting Lv ◽  
Guangyong Sun ◽  
Shuxiang Li ◽  
Weijia Duan ◽  
...  
Keyword(s):  
T Cells ◽  
Flow Cytometric Analysis ◽  
Γδ T Cells ◽  
Absolute Number ◽  
Primary Biliary Cholangitis ◽  
Gamma Delta ◽  
Potential Marker ◽  
Hla Dr ◽  
Tnf Α ◽  
Elevated Expression

Abstract Background & Aims Gamma-delta (γδ) T cells are involved in the development of diverse liver and autoimmune diseases, whereas the role of γδ T cells in primary biliary cholangitis (PBC) remains unclear. Methods We analyzed the number, phenotypes, and functional molecules of γδ T cells in PBC patients (n = 74) and sex- and age-matched healthy controls (HCs) (n = 74) by flow cytometric analysis. Results We identified two distinct functional subsets of circulating γδ T cells according to the CD3/TCRγδ complex: the TCRγδhigh and TCRγδlow subsets. Approximately three-quarters of cells in the TCRγδhigh subset were Vδ1 T cells, while Vδ2 T cells were enriched in the TCRγδlow subset in HCs. The frequency and absolute number of circulating TCRγδlow cells was significantly decreased in PBC patients compared with HCs (p < 0.001). Furthermore, the frequency of TCRγδlow cells was negatively correlated with disease severity and positively correlated with the ursodeoxycholic acid response. TCRγδlow cells exhibited a similar apoptotic and proliferative phenotype but enhanced liver-homing chemokine receptor (CXCR6) expression in PBC patients compared with HCs. In addition, both TCRγδhigh and TCRγδlow subsets were more activated in PBC compared with HCs, characterized by elevated expression levels of CD69 and HLA-DR. Finally, we found an increased granzyme B (GZMB) production and similar IFN-γ and TNF-α production of TCRγδlow cells in PBC patients compared with HCs. Conclusion The TCRγδlow subset might be a potential marker for disease progression and treatment response in PBC, which may play a crucial role in liver injury through increased CXCR6 expression and GZMB production.

scholarly journals Differential Activation of V γ4V δ1 and V γ9V δ2 Cord Blood Derived Gamma Delta T Cells upon Exposure to EBV-Lcl and K562 Cells

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2790-2790
Author(s):  
Jeremy Wee Kiat Ng ◽  
Joey Lai ◽  
Tony Kiat Hon Lim ◽  
William YK Hwang ◽  
Shang Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Single Cell ◽  
Γδ T Cells ◽  
Rapid Expansion ◽  
Leukemia Cell Line ◽  
Γδ T Cell ◽  
Gamma Delta

Abstract Gamma-delta (γδ) T cells have emerged as a promising candidate for adoptive cellular immunotherapy. To harness and maximize the anti-leukemia properties of these cells, we sort to comprehensively profile the transcriptomic signatures and immune repertoire of in vitro expanded γδ T cell products. Given the reported diverse TCR γδ repertoire and naïve nature of γδ T cells found in human cord blood (CB γδ), we serially track the molecular and cellular changes in these cells upon activation in expansion cultures. Based on the established viral reactivities of γδ T cell as well as prior studies showing their cross reactivities against leukemia and cancer cells, we had previously shown that stimulating CB γδ with an irradiated EBV-LCL feeder cell-based rapid expansion protocol (REP) is capable of generating cell products with potent and specific cytotoxicity against human AML cells. In the present study, using single cell RNA sequencing (scRNA-seq) coupled with single cell TCR γδ repertoire analysis, we compared the transcription signatures between our REP expanded γδ T cell (REP γδ) and non-manipulated γδ T cells reported in literatures, showing the progressive acquisition of an adult PB derived γδ T cell (PB γδ)-like cell states. Time course analysis demonstrated complex T cell activation and maturation trajectories correlating with variable level of clonal induction throughout the course of in vitro expansion. At the end of expansion, the harvested REP γδ are predominantly of the V γ4V δ1 subtype. Nevertheless, upon exposing REP γδ to target leukemia cell line K562, outgrowth of other non-V γ4V δ1 as well as the semi-invariant V γ9V δ2 cells were observed. Taken together, our data shows that as CB γδ expand and differentiate in culture, they adopt an adult PB γδ-like program. More importantly, our data highlights the rich clonal composition of in vitro expanded CB γδ, with different clonotypes being variably activated upon exposure to different stimuli. Such characteristics can potentially overcome the challenges of cancer heterogeneity and cell persistence, with the potential of improving outcomes in cell immunotherapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Decreased Frequencies of Gamma/Delta T Cells Expressing Th1/Th17 Cytokine, Cytotoxic, and Immune Markers in Latent Tuberculosis-Diabetes/Pre-Diabetes Comorbidity

2021 ◽  
Vol 11 ◽  
Author(s):  
Gokul Raj Kathamuthu ◽  
Nathella Pavan Kumar ◽  
Kadar Moideen ◽  
Pradeep A. Menon ◽  
Subash Babu
Keyword(s):  
T Cells ◽  
Latent Tuberculosis ◽  
Γδ T Cells ◽  
Positive Control ◽  
Gamma Delta ◽  
Immune Markers ◽  
Antigen Stimulation ◽  
Significant Difference ◽  
Control Antigen ◽  
Th17 Cytokine

Antigen-specific gamma-delta (γδ) T cells are important in exhibiting anti-mycobacterial immunity, but their role in latent tuberculosis (LTB) with diabetes mellitus (DM) or pre-DM (PDM) and non-DM comorbidities have not been studied. Thus, we have studied the baseline, mycobacterial (PPD, WCL), and positive control antigen-stimulated γδ T cells expressing Th1 (IFNγ, TNFα, IL-2) and Th17 (IL-17A, IL-17F, IL-22) cytokine as well as cytotoxic (perforin [PFN], granzyme [GZE B], granulysin [GNLSN]) and immune (GMCSF, PD-1, CD69) markers in LTB (DM, PDM, NDM) comorbidities by flow cytometry. In the unstimulated (UNS) condition, we did not observe any significant difference in the frequencies of γδ T cells expressing Th1 and Th17 cytokine, cytotoxic, and immune markers. In contrast, upon PPD antigen stimulation, the frequencies of γδ T cells expressing Th1 (IFNγ, TNFα) and Th17 (IL-17F, IL-22) cytokine, cytotoxic (PFN, GZE B, GNLSN), and immune (CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Similarly, upon WCL antigen stimulation, the frequencies of γδ T cells expressing Th1 (TNFα) and Th17 (IL-17A, IL-22) cytokine, cytotoxic (PFN), and immune (PD-1, CD69) markers were significantly diminished in LTB DM and/or PDM individuals compared to LTB NDM individuals. Finally, upon P/I stimulation we did not observe any significant difference in the γδ T cell frequencies expressing cytokine, cytotoxic, and immune markers between the study populations. The culture supernatant levels of IFNγ, TNFα, and IL-17A cytokines were significantly increased in LTB DM and PDM after stimulation with Mtb antigens compared to LTB NDM individuals. Therefore, diminished γδ T cells expressing cytokine, cytotoxic, and other immune markers and elevated levels of cytokines in the supernatants is a characteristic feature of LTB PDM/DM co-morbidities.

scholarly journals Gene expression of T lymphocytes of gravid cows during preimplantation

2013 ◽  
Vol 82 (2) ◽  
pp. 131-134 ◽  
Author(s):  
Yousuke Maeda ◽  
Kana Yamamoto ◽  
Hiromichi Ohtsuka ◽  
Takaaki Ando ◽  
Michiko Tomioka ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Γδ T Cells ◽  
Interferon Γ ◽  
T Cell Subsets ◽  
Interleukin 4 ◽  
Blocking Factor

An interaction between the conceptus and the immune system of animals is important during implantation. The aim of this study was to clarify the gene expression of T cell subsets in gravid cows during the preimplantation period. Peripheral blood from 14 Holstein dairy cows was taken 14 days after artificial insemination. Based on the gravidity, cows were divided into gravid (n = 8) and nongravid (n = 6) groups. Mononuclear cells from peripheral blood were stimulated with phytohaemagglutinin and then CD4+, CD8+, and WC1+ γδ T cell subsets were isolated using magnetic cell sorting. The expression of interferon γ, interleukin 4, and progesterone induced blocking factor were determined using real-time PCR. The expression of interleukin 4 and progesterone induced blocking factor was significantly higher in WC1+ γδ T cells from gravid cows. In addition, interleukin 4 expression in WC1+ γδ T cells from gravid cows was significantly higher than that in CD4+ and CD8+ T cells. This study describes for the first time the important role of WC1+ γδ T cells during the preimplantation period in cows.

scholarly journals Bovine gamma/delta T cells are stimulated by bovine coronavirus antigens identified by a soluble T cells receptor

2017 ◽  
Vol 73 (7) ◽  
pp. 412-417
Author(s):  
Felix N. Toka
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Γδ T Cells ◽  
In Vitro Study ◽  
Fold Increase ◽  
In Vitro Assays ◽  
Gamma Delta ◽  
Bovine Coronavirus ◽  
Gm Csf

Gamma/delta (γδ) T cells in cattle account for an abundant T cell population. However, little is known regarding the function of γδ T cells as immune cells compared to αβ T cells. Not many pathogen-related antigens have been defined and known to stimulate γδ T cells. To address this information gap, we constructed a soluble receptor for bovine γδ T cells (sγδTCR) that was later used to identify two proteins (156 kDa and 102 kDa) or protein fragments expressed by bovine coronavirus (BCov). The molecular weight of the larger protein suggests it could be the spike glycoprotein of BCov. Subsequently, we used the identified viral proteins to study the reactivity of bovine γδ T cells. In vitro assays showed that purified preparations of the two proteins stimulated WC1+ γδ T cells isolated from cattle. A 4-fold increase in IFN production and a significantly higher expression of MHC class II was observed. However, these viral ligands could not stimulate γδ T cells to synthesize IL-8 or GM-CSF, known to be produced by γδ T cells when stimulated with bacterial antigens. Although the γδ T cells assessed here appeared activated by way of IFN and MHC II expression, surface markers such as CD2, CD25, CD44, CD62L and CD335 were not expressed at significant levels. Further, the activation elicited by viral ligands was not sufficient to induce cytotoxic capability in γδ T cells in vitro as measured by a flow cytometry-based cytotoxicity assay. This in vitro study shows that WC1+ γδ T cells can directly recognize viral antigen

scholarly journals Association between Serum Heat Shock Proteins and Gamma-Delta T Cells—An Outdated Clue or a New Direction in Searching for an Anticancer Strategy? A Short Report

2021 ◽  
Vol 11 (16) ◽  
pp. 7325
Author(s):  
Dorota Pawlik-Gwozdecka ◽  
Justyna Sakowska ◽  
Maciej Zieliński ◽  
Magdalena Górska-Ponikowska ◽  
Francesco Cappello ◽  
...  
Keyword(s):  
T Cells ◽  
Strong Association ◽  
Γδ T Cells ◽  
Diagnostic Methods ◽  
Enzyme Linked Immunosorbent Assay ◽  
Short Report ◽  
Gamma Delta ◽  
Childhood All ◽  
Hla Dr ◽  
Shock Proteins

HSPs demonstrate a strong association with gamma-delta (γδ) T cells. Most of the studies regarding interactions between the parameters were conducted in the 1990s. Despite promising results, the concept of targeting γδ T cells by HSPs seems to be a forgotten direction due to potent non-peptidic phosphoantigens rather than HSPs have been found to be the essential stimulatory components for human γδ cells. Currently, with greater knowledge of lymphocyte diversity, and more accurate diagnostic methods, we decided to study the correlation once again in the neoplastic condition. Twenty-one children with newly diagnosed acute lymphoblastic leukaemia (ALL) were enrolled on the study. Serum HSP90 concentrations were evaluated by an enzyme-linked immunosorbent assay (ELISA), subsets of γδ T cells (CD3+ γδ, CD3+ γδ HLA/DR+, CD4+ γδ and CD8+ γδ) by flow cytometry. We have shown statistically relevant correlations between serum HSP90 and CD3+ HLA/DR+ γδ T cells in paediatric ALL at diagnosis (R = 0.53, p < 0.05), but not after induction chemotherapy. We also have demonstrated decreased levels of both serum HSP90 and CD3+ HLA/DR+ γδ T cells before treatment, which may indirectly indicate dose-dependent unknown interaction between the parameters. The results of our study may be a good introduction to research on the association between HSPs and CD3+ HLA/DR+ γδ T cells, which could be an interesting direction for the development of anti-cancer strategies, not just for childhood ALL.

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