Anti-Tumor Actions of Trametes Versicolor Extract Polysaccharide K Include Activation of Dendritic Cells and Gamma Delta T Cells

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
CA Wenner ◽  
C Inatsuka ◽  
T Davis Smith ◽  
M Sasagawa ◽  
MR Martzen ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Trametes Versicolor ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Polysaccharide K

Dendritic Cells Can Be Primed to Concurrently Activate Both Unconventional Gamma/delta and Conventional alpha/beta T Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3893-3893
Author(s):  
Francesca Fiore ◽  
Barbara Castella ◽  
Barbara Nuschak ◽  
Raffaello Bertieri ◽  
Sara Mariani ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Adoptive Cell Therapy ◽  
Effector Memory ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta

Abstract Vgamma9/Vdelta2 (gamma/delta) T cells represent the major subset of unconventional T cells circulating in the peripheral blood. Gamma/delta T cells play a major role in immune defenses against microbes, stressed cells and tumor cells. This property is based on their capability to naturally recognize phosphoantigens (pAgs), which are produced via the mevalonate (Mev) or the DOXP pathway in mammalian and nonmammalian cells, and induced self-ligands, which are de novo expressed or upregulated on the surface of stressed or tumor cells. Interestingly, gamma/delta T cells can also be activated by aminobisphosphonates (ABP)-treated monocytes. We have previously shown that ABP specifically target the Mev pathway of monocytes and induce the accumulation of phosphorylated Mev metabolites naturally recognized by gamma/delta T cells. The aim of this work was to determine whether ABP-treated dendritic cells (DC) can also activate gamma/delta T cells and whether this activation, if any, is detrimental or beneficial to the generation of antigen (Ag)-specific MHC-restricted immune responses mediated by conventional alpha/beta T cells. To this end, we have generated highly purified immature (iDC) and mature DC (mDC) from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol is the most potent ABP currently available for clinical use. Zol treatment did not affect the phenotype and immunostimulatory properties of iDC and mDC. Zol-treated iDC and mDC induced a rapid and vigorous expansion of central memory and effector memory gamma/delta T cells. Zol-treated iDC were more potent inducers of gamma/delta T-cell activation than mDC and monocytes. Activated gamma/delta T cells displayed antitumor activity and expressed on the cell surface the appropriate antigen repertoire to target secondary lymphoid organs and exert costimulatory activity on conventional alpha/beta T cells. Indeed, an in vitro model showed that antigen-specific MHC-restricted immune responses againt the influenza matrix peptide were significantly improved by the concurrent activation of gamma/delta T cells. This is the first report showing that: 1) DC can simultaneously be primed to activate both gamma/delta and alpha/beta T cells; 2) the former act as cellular adjuvants for the development of adaptive immune responses. In conclusion, large numbers of gamma/delta T cells with effector and costimulatory activities can rapidly be generated by Zol-treated iDC/mDC. This strategy is worth of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.

Low Blood Counts of Memory/Effector CD8 T Cells, Gamma/Delta T Cells, Memory B Cells and Plasmacytoid Dendritic Cells and High Counts of Th2 Cells in Systemic Sclerosis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4917-4917
Author(s):  
Jan Storek ◽  
Rob Woolson ◽  
Paul K. Wallace ◽  
Gregory Sempowski ◽  
Peter A. McSweeney ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Systemic Sclerosis ◽  
B Cells ◽  
Cd8 T Cells ◽  
Plasmacytoid Dendritic Cells ◽  
Memory B Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Memory Cd8 T Cells

Abstract Abstract 4917 Introduction: Systemic sclerosis (SSc) is presumed to result from aberrant activation of autoreactive T cells. However, the exact pathogenesis of SSc is not known. Patients and Methods: To contribute to the understanding of the immunopathology of systemic sclerosis (SSc), we compared blood counts of multiple lymphocyte subsets between 20 adult SSc patients not treated with immunomodulatory drugs and healthy controls. The patients had to fit entry criteria for SCOT trial (Scleroderma – Cyclophosphamide or Transplantation?, www.sclerodermatrial.org), i.e, 1. symptoms for no longer than 5 years (except for Raynaud's phenomenon), 2. diffuse scleroderma, and 3. either moderate lung involvement (forced vital capacity (FVC) or diffusion of carbon monoxide (DLCO) between 45 and 70% predicted) or moderate kidney involvement (history of hypertensive renal crisis, but normal renal function at study entry). Multiparameter flow cytometry was used for the determination of the lymphocyte subset counts. Results: Counts of the following subsets were significantly lower in the patients compared to the controls: total T cells (median 1316 vs 2088/ul, p=0.015), total CD8 T cells (273 vs 580/ul, p<0.001), central memory CD8 T cells (23 vs 87/ul, p<0.001), effector memory CD8 T cells (17 vs 39/ul, p=0.015), effector CD8 T cells (28 vs 68/ul, p=0.001), gamma/delta T cells (31 vs 77/ul, p<0.001), switched (IgM/DàIgG/A isotype switched) memory B cells (6 vs 26/ul, p<0.001), non-switched memory B cells (7 vs 17/ul, p=0.004), and plasmacytoid dendritic cells (2 vs 6/ul, p=0.002). Counts of Th2-biased (producing interleukin-4 upon polyclonal stimulation) CD4 as well as CD8 T cells were significantly higher in the patients compared to the controls (248 vs 139/ul for CD4, p=0.002, and 259 vs 164/ul for CD8, p<0.001). Conclusion: Immunopathology of SSc is complex. Low blood counts of memory/effector CD8 T cells, gamma/delta T cells, memory B cells and plasmacytoid dendritic cells and Th2-biased T cells may play a role in the pathogenesis of SSc. However, cause and effect relations need to be established. Given previous reports of increased numbers of CD8 and gamma/delta T cells in the affected tissues of patients with systemic sclerosis and increased numbers of plasmacytoid dendritic cells in the affected tissues of patients with autoimmune diseases (compared to healthy individuals) (Prescott RJ et al: J Pathol 166 (1992) 255–63, Atamas SP et al: Arthritis Rheum 42 (1999) 1168–78, Giacomelli R et al: Arthritis Rheum 41 (1998) 327–34, Yurovski VV et al: J Immunol 153 (1994) 881–91, Nestle FO et al: J Exp Med 202 (2005) 35–43, Farkas L et al: Am J Pathol 159 (2001) 237–43), it is possible that the low blood counts of CD8 T cells, gamma/delta T cells and plasmacytoid dendritic cells result from redistribution of these cells from blood to affected tissues. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Gamma delta T cells are activated by polysaccharide K (PSK) and contribute to the anti-tumor effect of PSK

2013 ◽  
Vol 62 (8) ◽  
pp. 1335-1345 ◽  
Author(s):  
Carol Inatsuka ◽  
Yi Yang ◽  
Ekram Gad ◽  
Lauren Rastetter ◽  
Mary L. Disis ◽  
...  
Keyword(s):  
T Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Polysaccharide K

scholarly journals Novel Immune-Related Genetic Expression for Primary Sjögren's Syndrome

2022 ◽  
Vol 8 ◽  
Author(s):  
Jiajia Cui ◽  
Hui Li ◽  
Tianling Wang ◽  
Qin Shen ◽  
Yuanhao Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dendritic Cells ◽  
B Cells ◽  
Primary Sjögren’S Syndrome ◽  
Memory B Cells ◽  
Gamma Delta T Cells ◽  
Ppi Network ◽  
Gamma Delta ◽  
Key Genes

Objective: To identify novel immune-related genes expressed in primary Sjögren's syndrome (pSS).Methods: Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. The differences in immune cell proportion between normal and diseased tissues were compared, weighted gene co-expression network analysis was conducted to identify key modules, followed by a protein–protein interaction (PPI) network generation and enrichment analysis. The feature genes were screened and verified using the GEO datasets and quantitative real-time PCR (RT-qPCR).Results: A total of 345 DEGs were identified, and the proportions of gamma delta T cells, memory B cells, regulatory T cells (Tregs), and activated dendritic cells differed significantly between the control and pSS groups. The turquoise module indicated the highest correlation with pSS, and 252 key genes were identified. The PPI network of key genes showed that RPL9, RBX1, and RPL31 had a relatively higher degree. In addition, the key genes were mainly enriched in coronavirus disease-COVID-2019, hepatitis C, and influenza A. Fourteen feature genes were obtained using the support vector machine model, and two subtypes were identified. The genes in the two subtypes were mainly enriched in the JAK-STAT, p53, and toll-like receptor signaling pathways. The majority of the feature genes were upregulated in the pSS group, verified using the GEO datasets and RT-qPCR analysis.Conclusions: Memory B cells, gamma delta T cells, Tregs, activated dendritic cells, RPL9, RBX1, RPL31, and the feature genes possible play vital roles in the development of pSS.

scholarly journals Systematic analysis of tumor-infiltrating immune cells in human endometrial cancer: a retrospective study

2019 ◽  
Author(s):  
Xi Zhou ◽  
Zhengjiang Ling ◽  
Bing Yang
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Endometrial Cancer ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Expression Profiles ◽  
Response To Therapy ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Memory Cd4 T Cells

AbstractObjectiveThe prognostic effect of tumor-infiltrating immune cells (TIICs) on endometrial cancer (EMC) has not been extensively investigated. In the present study, we systematically analyzed the role of TIICs in EMC development.MethodsPatient data were downloaded from The Cancer Genome Atlas (TCGA). We comprehensively analyzed TIIC population in EMC tissue and their role in EMC progression and prognosis by using a deconvolution algorithm (CIBERSORT) and clinically annotated expression profiles.ResultsThe proportions of gamma delta T cells, resting NK cells, M1 macrophages, and resting mast cells were significantly different in normal endometrium and EMC tissue. The proportion of CD8+ T cells, resting memory CD4 T cells, and M0 macrophages was reversed middle correlated. The proportion of resting dendritic cells, resting memory CD4 T cells, and T regulatory cells (Tregs) decreased in accordance with the cancer cell differentiation grade (G); the lower proportion of activated dendritic cells and gamma delta T cells and higher proportion of Tregs predicted longer EMC survival time and vice versa. The low proportion of gamma delta T cells indicated better response to therapy.ConclusionCollectively, our data suggested subtle differences in the cellular composition of TIICs in EMC, and these differences were likely to be important determinants of both prognosis and therapy of EMC.

scholarly journals Enhancement of Anti-tumor Cytotoxicity of Expanded .GAMMA..DELTA. T Cells by Stimulation with Monocyte-derived Dendritic Cells

2007 ◽  
Vol 47 (2) ◽  
pp. 61-72 ◽  
Author(s):  
Anri Saito ◽  
Miwako Narita ◽  
Ayumi Yokoyama ◽  
Norihiro Watanabe ◽  
Nozomi Tochiki ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Tumor Cytotoxicity

600 In vitro anticancer and immunomodulatory activities of NBT-167, a dimer of resveratrol

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A635-A635
Author(s):  
Jeffrey Zhang ◽  
Everett Henry ◽  
L Harris Zhang ◽  
Wanying Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Immune Cells ◽  
Cell Killing ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Raw264.7 Macrophages

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.

scholarly journals Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.

1994 ◽  
Vol 179 (1) ◽  
pp. 311-315 ◽  
Author(s):  
M K Perera ◽  
R Carter ◽  
R Goonewardene ◽  
K N Mendis
Keyword(s):  
T Cells ◽  
Plasmodium Vivax ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Gastrointestinal Symptoms ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Endemic Region ◽  
Gastrointestinal Pathology

The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+ phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescence or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of gamma/delta T cells (p &lt; 0.005 and &lt; 0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted &lt; or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of gamma/delta T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in gamma/delta T cells either during infection, even during paroxysms, or convalescence. The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of gamma/delta T cells in peripheral blood (r = 0.53, p &lt; 0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These findings suggest that gamma/delta T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.

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