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https://www.readbyqxmd.com/read/29899740/gmp-grade-manufacturing-of-t-cells-engineered-to-express-a-defined-%C3%AE-%C3%AE-tcr
#1
Trudy Straetemans, Guido J J Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M Dos Santos, Anna D D van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29867959/thymic-program-directing-the-functional-development-of-%C3%AE-%C3%AE-t17-cells
#2
REVIEW
Youenn Jouan, Emmanuel C Patin, Maya Hassane, Mustapha Si-Tahar, Thomas Baranek, Christophe Paget
γδT cells comprise a unique T cell sublineage endowed with a wide functional repertoire, which allow them to play important-sometimes opposite-roles in many immune responses associated with infection, cancer, and inflammatory processes. This is largely dependent on the existence of pre-programmed discrete functional subsets that differentiate within the thymus at specific temporal windows of life. Since they represent a major early source of interleukin-17A in many models of immune responses, the γδT17 cell population has recently gained considerable interest...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29867952/fish-lymphocytes-an-evolutionary-equivalent-of-mammalian-innate-like-lymphocytes
#3
REVIEW
Giuseppe Scapigliati, Anna M Fausto, Simona Picchietti
Lymphocytes are the responsible of adaptive responses, as they are classically described, but evidence shows that subpopulations of mammalian lymphocytes may behave as innate-like cells, engaging non-self rapidly and without antigen presentation. The innate-like lymphocytes of mammals have been mainly identified as γδT cells and B1-B cells, exert their activities principally in mucosal tissues, may be involved in human pathologies and their functions and tissue(s) of origin are not fully understood. Due to similarities in the morphology and immunobiology of immune system between fish and mammals, and to the uniqueness of having free-living larval stages where the development can be precisely monitored and engineered, teleost fish are proposed as an experimental model to investigate human immunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29797009/isolating-immune-cells-from-mouse-embryonic-skin
#4
Ambika S Kurbet, Srikala Raghavan
Skin is the primary barrier against the external environment and develops a robust immune network for its surveillance. The origin of the resident immune cells of the skin has become a focus of interest over past a decade. Fate mapping studies have revealed that the macrophages home into the skin as early as E12.5 and are derived from the yolk sac and fetal liver. The resident γδT cells are born in the thymus and home to the skin by E16.5. Recent work from our lab has shown that the embryonic macrophages can actively remodel the extracellular matrix in skin suggesting that the skin immune system can be activated long before exposure to foreign antigens...
May 24, 2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29740432/unique-and-common-features-of-innate-like-human-v%C3%AE-2-%C3%AE-%C3%AE-t-cells-and-mucosal-associated-invariant-t-cells
#5
Nicholas M Provine, Benedikt Binder, Michael E B FitzPatrick, Anita Schuch, Lucy C Garner, Kate D Williamson, Bonnie van Wilgenburg, Robert Thimme, Paul Klenerman, Maike Hofmann
Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans that can be activated in a TCR-independent manner by inflammatory and antiviral cytokines. In humans, the capacity for TCR-independent activation is functionally linked to a transcriptional program that can be identified by the expression of the C-type lectin receptor, CD161. In addition to MAIT cells, it has been demonstrated that a subset of γδT cells expresses CD161 and can be activated by TCR-independent cytokine stimulation...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29730909/-establishment-of-the-culture-system-of-%C3%AE-%C3%AE-t-cells-in-vitro-and-the-anti-tumor-effect
#6
L Xie, W Chen, L Wang, M Cheng, S L Hu, G Shen
Objective: To establish the culture technique for culturing γδ T cells in vitro and evaluate the basic characteristics, security and anti-tumor effect of the cultured γδ T cells. Methods: Phytohemagglutinin, zoledronic acid, interleukin-2 and interleukin -7 were used to induce the abundant expansion of peripheral blood mononuclear cells in vitro . Flow cytometry assay, in vitro killing assay and mouse model of human lung cancer were also adopted to assess the characteristics and the anti-tumor effect of cultured γδ T cells...
April 23, 2018: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/29721384/low-dose-gemcitabine-increases-the-cytotoxicity-of-human-v%C3%AE-9v%C3%AE-2-t-cells-in-bladder-cancer-cells-in-vitro-and-in-an-orthotopic-xenograft-model
#7
Teruki Shimizu, Mako Tomogane, Masatsugu Miyashita, Osamu Ukimura, Eishi Ashihara
Human γδT cell immunotherapy is well tolerated and has shown promising results in clinical trials; however, its antitumor efficacy is limited, including results in solid tumors. Ex-vivo expanded γδT cell stimulated by zoledronic acid (ZOL) activates the γδT cell subpopulation of so called Vγ9Vδ2 T cells. To improve the clinical outcomes of Vγ9Vδ2 T cell (abbreviated as γδT cell here) immunotherapy, we aimed to increase the cytotoxicity of γδT cells by focusing on two issues: recognition of tumor cells by γδT cells and the effector (γδT cell)-to-target (tumor cell) (E/T) ratio...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29718261/mice-lacking-all-of-the-skint-family-genes
#8
Tomoya Narita, Takeshi Nitta, Sachiko Nitta, Tadashi Okamura, Hiroshi Takayanagi
γδT cells develop in the thymus and play important roles in protection against infection and tumor development, but the mechanisms by which the thymic microenvironment supports γδT cell differentiation remain largely unclear. Skint1, a B7-related protein expressed in thymic epithelial cells, was shown to be essential for the development of mouse Vγ5Vδ1 γδT cells. The Skint family in mouse consists of 11 members, Skint1-11. Here we generated mutant mice lacking the entire genomic region that contains all of the Skint genes...
April 26, 2018: International Immunology
https://www.readbyqxmd.com/read/29675018/contribution-to-tumor-angiogenesis-from-innate-immune-cells-within-the-tumor-microenvironment-implications-for-immunotherapy
#9
REVIEW
Adriana Albini, Antonino Bruno, Douglas M Noonan, Lorenzo Mortara
The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs) and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF) and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29566909/nafld-helicobacter-species-and-the-intestinal-microbiome
#10
REVIEW
Natalia Castaño-Rodríguez, Hazel M Mitchell, Nadeem O Kaakoush
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. It is well-accepted that gut dysbiosis is associated with NAFLD, however, there is some conflicting evidence regarding the nature of these alterations. Infection with Helicobacter species, mainly H. pylori, has also been associated with increased NAFLD risk, however, some studies have failed to reproduce this finding. Further studies including large study samples and standardised procedures for microbiota analyses, H...
December 2017: Best Practice & Research. Clinical Gastroenterology
https://www.readbyqxmd.com/read/29512904/ebv-transformation-induces-overexpression-of-hmsh2-3-6-on-b-lymphocytes-and-enhances-%C3%AE-%C3%AE-t-cell-mediated-cytotoxicity-via-tcr-and-nkg2d
#11
Yu-Mei Dai, Hai-Ying Liu, Yun-Feng Liu, Yuan Zhang, Wei He
The engagement of Epstein-Barr virus (EBV)-induced protein ligands in γδ T-cell-mediated anti-EBV immunity, especially in EBV-associated B-cell malignancies, has not been fully elucidated. Previously we reported the overexpression of human MutS homologue 2 (hMSH2), a stress-inducible protein ligand for human γδ T-cells, on EBV-transformed B lymphoblastic cell lines (B-LCLs). In this study, we first generated EBV-transformed B-LCLs from peripheral blood mononuclear cells of healthy volunteers with B95-8 cellular supernatant and cyclosporine A...
March 7, 2018: Immunology
https://www.readbyqxmd.com/read/29476737/serum-levels-of-il-17-are-elevated-in-patients-with-acute-gouty-arthritis
#12
Yang Liu, Qianzi Zhao, Yuxin Yin, Michael A McNutt, Tie Zhang, Yongtong Cao
Acute gouty arthritis (AGA) is one of the most common forms of auto-inflammatory arthritis. IL-17 is a key proinflammatory cytokine which has been implicated in several autoimmune diseases. However, to date little is known about the role of IL-17 in AGA. In the present study, we show that serum IL-17 levels are significantly elevated in AGA patients early in the onset of symptoms of gout, and decrease gradually as symptoms diminish. Correlation analysis indicated that IL-17 expression is not only positively correlated with disease activity, but is also correlated with serum levels of IL-1β which plays a critical role in the differentiation of IL-17- γδT cells into IL-17+ γδT cells...
March 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29469612/the-atypical-chemokine-receptor-ackr2-drives-pulmonary-fibrosis-by-tuning-influx-of-ccr2-and-ccr5-ifn%C3%AE-producing-%C3%AE-%C3%AE-t-cells-in-mice
#13
Remo Castro Russo, Benedetta Savino, Massimiliano Mirolo, Chiara Buracchi, Giovanni Germano, Achille Anselmo, Luca Zammataro, Fabio Pasqualini, Alberto Mantovani, Massimo Locati, Mauro M Teixeira
RATIONALE: Chemokines coordinate lung inflammation and fibrosis by acting on chemokine receptors expressed on leukocytes and other cell types. Atypical chemokine receptors (ACKRs) bind, internalize and degrade chemokines, tuning homeostasis and immune responses. ACKR2 recognizes and decreases levels of inflammatory CC chemokines. The role of ACKR2 in fibrogenesis is unknown. OBJECTIVE: Investigate the role of ACKR2 in the context of pulmonary fibrosis. METHODS: The effects of ACKR2 expression and deficiency during inflammation and fibrosis were analyzed using a bleomycin-model of fibrosis, ACKR2-deficient mice, bone marrow chimeras and antibody-mediated leukocyte depletion...
February 22, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29434775/il-25-promotes-th2-bias-by-upregulating-il-4-and-il-10-expression-of-decidual-%C3%AE-%C3%AE-t-cells-in-early-pregnancy
#14
Yuan Zhang, Ying Wang, Ming-Qing Li, Jie Duan, Deng-Xuan Fan, Li-Ping Jin
Decidual immune cells (DICs), consisting of both innate and adaptive immune cells, have a pivotal role in maintaining immune tolerance for normal pregnancy. Our previous study demonstrated that interleukin (IL)-25 stimulates the proliferation of decidual stromal cells (DSCs) in an autocrine manner. However, the role of IL-25 in functional regulation of DICs is largely unknown. Flow cytometry was used to analyze the expression of IL-25 and its receptor (IL-17RB) in DICs, and the effect of IL-25 on the expression of Ki-67, IL-4, IL-10, interferon (IFN)-γ and transforming growth factor (TGF)-β in decidual γδT cells...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29401165/hmgn2-an-antitumor-effector-molecule-of-%C3%AE-%C3%AE-t-cells
#15
Jiao Chen, Yaping Fan, Bomiao Cui, Xiaoying Li, Yu Yu, Yue Du, Qianming Chen, Yun Feng, Ping Zhang
γδT cells function in the regulation of T-cell activation in cancer and have been identified as a novel target for cancer immunotherapy. Activated γδT cells release a series of cytotoxic molecules-including granulysin, perforin, Fas/Fas ligand (Fas-L), and granzymes A and B-to kill target cells. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2), which is expressed at a high level in activated CD8T cells, is an antitumor effector molecule of CD8T cells. In the present study, we examined the expression and antitumor effects of HMGN2 in γδT cells...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29400706/profiling-the-pattern-of-the-human-t-cell-receptor-%C3%AE-%C3%AE-complementary-determinant-region-3-repertoire-in-patients-with-lung-carcinoma-via-high-throughput-sequencing-analysis
#16
Hui Chen, Mingjin Zou, Da Teng, Yu Hu, Jianmin Zhang, Wei He
γδ T cells function as sentinels in early host responses to infections and malignancies. Specifically, γδ T cells recognize tumor-associated stress antigens via T-cell receptor (TCR) γδ and play important roles in the antitumor immune response. In this study, we characterized the pattern of the human TCR γδ complementary determinant region 3 (CDR3) repertoire in patients with lung carcinoma (LC) via high-throughput sequencing. The results showed that the diversity of CDR3δ was significantly reduced, and that of CDR3γ was unchanged in LC patients compared with healthy individuals; in addition, LC patients shared significantly more CDR3δ sequences with each other than healthy individuals...
February 5, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29399441/nk-cells-and-%C3%AE-%C3%AE-t-cells-for-relapse-protection-after-allogeneic-hematopoietic-cell-transplantation-hct
#17
Moniek A de Witte, Jürgen Kuball, Jeffrey S Miller
Purpose of review: The outcome of allogeneic stem cell transplantation (allo-HCT) is still compromised by relapse and complications. NK cells and γδT cells, effectors which both function through MHC-unrestricted mechanisms, can target transformed and infected cells without inducing Graft-versus-Host Disease (GVHD). Allo-HCT platforms based on CD34+ selection or αβ-TCR depletion result in low grades of GVHD, early immune reconstitution (IR) of NK and γδT cells and minimal usage of GVHD prophylaxis...
December 2017: Current Stem Cell Reports
https://www.readbyqxmd.com/read/29371380/the-inflammatory-cell-landscape-in-the-lungs-of-patients-with-idiopathic-pulmonary-arterial-hypertension
#18
Leigh M Marsh, Katharina Jandl, Gabriele Grünig, Vasile Foris, Mina Bashir, Bahil Ghanim, Walter Klepetko, Horst Olschewski, Andrea Olschewski, Grazyna Kwapiszewska
Increasing evidence points towards an inflammatory component underlying pulmonary hypertension. However, the conclusive characterisation of multiple inflammatory cell populations in the lung is challenging due to the complexity of marker specificity and tissue inaccessibility. We used an unbiased computational flow cytometry approach to delineate the inflammatory landscape of idiopathic pulmonary arterial hypertension (IPAH) and healthy donor lungs.Donor and IPAH samples were discriminated clearly using principal component analysis to reduce the multidimensional data obtained from single-cell flow cytometry analysis...
January 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29320890/chimeric-antigen-receptors-in-different-cell-types-new-vehicles-join-the-race
#19
Dennis C Harrer, Jan Dörrie, Niels Schaft
Adoptive cellular therapy has evolved into a powerful force in the battle against cancer, holding promise for curative responses in patients with advanced and refractory tumors. Autologous T cells, reprogrammed to target malignant cells via the expression of a chimeric antigen receptor (CAR) represent the frontrunner in this approach. Tremendous clinical regressions have been achieved using CAR-T cells against a variety of cancers both in numerous preclinical studies and in several clinical trials, most notably against acute lymphoblastic leukemia, and resulted in a very recent United States Food and Drug Administration approval of the first CAR-T-cell therapy...
February 27, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29310916/chimeric-antigen-receptor-engineered-human-gamma-delta-t-cells-enhanced-cytotoxicity-with-retention-of-cross-presentation
#20
Anna Capsomidis, Gabriel Benthall, Heleen H Van Acker, Jonathan Fisher, Anne M Kramer, Zarah Abeln, Yvonne Majani, Talia Gileadi, Rebecca Wallace, Kenth Gustafsson, Barry Flutter, John Anderson
Gamma delta T (γδT) lymphocytes are primed for rapid function, including cytotoxicity toward cancer cells, and are a component of the immediate stress response. Following activation, they can function as professional antigen-presenting cells. Chimeric antigen receptors (CARs) work by focusing T cell function on defined cell surface tumor antigens and provide essential costimulation for robust activation. Given the natural tropism of γδT cells for the tumor microenvironment, we hypothesized that their transduction with CARs might enhance cytotoxicity while retaining their ability to migrate to tumor and act as antigen-presenting cells to prolong the intratumoral immune response...
February 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
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