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T E Kononova, O I Urazova, V V Novitskii, I E Esimova, E G Churina
The study of subpopulation structure of IFNγ-producing T cells in patients with pulmonary tuberculosis revealed a decrease in the number of CD3+ IFNγ+ cells against the background of significantly increased IFNγ secretion in vitro irrespective of the clinical form of the disease and drug sensitivity of M. tuberculosis, most strongly expressed in case of the disseminated tuberculosis. In patients with infiltrative drug-sensitive and drug-resistant pulmonary tuberculosis, increased number of Th1/Th17 lymphocytes (CD4+ IFNγ+ IL-17A+ ) and, conversely, decreased number of blood γδT cells was detected...
July 12, 2018: Bulletin of Experimental Biology and Medicine
Jonathan Fisher, John Anderson
Sharing both innate and adaptive immune properties, γδT cells are attractive candidates for cellular engineering. As the cancer immunotherapy field becomes increasingly busy, orthogonal approaches are required to drive advancement. Engineering of alternative effector cell types such as γδT cells represents one such approach. γδT cells can be modified using many of the techniques used in αβT cell engineering, with the added advantage of innate-like tumor recognition and killing. Progress has been made in T-cell receptor transfer to and from γδT cells as well as in a number of chimeric antigen receptor-based strategies...
2018: Frontiers in Immunology
K Liu, Y X Shen, N Ling, Y Lei, P Hu, H Ren, M Chen
Objective: To observe the changes of γδT cells in the peripheral blood of patients with chronic hepatitis B (CHB) during pegylated interferon α-2a treatment, and to analyze the correlation between clinical indicators and curative effects. Methods: Peripheral blood of hepatitis B e antigen (HBeAg)-positive CHB patients were collected at different time points of Peg-IFNα-2a treatment, including 17 patients at 0 weeks, 20 patients at 12 weeks, 20 patients at 24 weeks, and 16 patients at 48 weeks. From these 11 patients, blood samples were frequently observed at 0, 12, 24, and 48 weeks of treatment...
May 20, 2018: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Xia Yang, Jing-Hong Zhang, Wang-Sheng Deng, Chao-Qian Li
We aimed to explore the imbalance between the T helper 17 γδT cells (γδT17) and the regulatory γδT cells (γδTreg) in asthmatic mice. Male Balb/c mice were randomly divided into the normal control group and the asthmatic model group. The asthmatic model group mice were intraperitoneally injected with the mixture of ovalbumin (OVA)/Al(OH)3 and then activated by exposure of the animals to OVA atomization. Airway hyperresponsiveness (AHR) was determined by a non-invasive lung function machine. Hematoxylin and eosin and Alcian blue-periodic acid Schiff staining were done for histopathological analysis...
July 10, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Tomohiro Fukaya, Takehito Fukui, Tomofumi Uto, Hideaki Takagi, Junta Nasu, Noriaki Miyanaga, Keiichi Arimura, Takeshi Nakamura, Haruhiko Koseki, Narantsog Choijookhuu, Yoshitaka Hishikawa, Katsuaki Sato
Disruption of skin homeostasis can lead to inflammatory cutaneous diseases resulting from the dysregulated interplay between epithelial keratinocytes and immune cells. Interleukin (IL)-22 signaling through membrane-bound IL-22 receptor 1 (IL-22R1) is crucial to maintain cutaneous epithelial integrity, and its malfunction mediates deleterious skin inflammation. While IL-22 binding protein (IL-22BP) binds IL-22 to suppress IL-22 signaling, how IL-22BP controls epithelial functionality to prevent skin inflammation remains unclear...
2018: Frontiers in Immunology
Eva C Schwaneck, Regina Renner, Lara Junker, Hermann Einsele, Ottar Gadeholt, Eva Geissinger, Stefan Kleinert, Michael Gernert, Hans-Peter Tony, Marc Schmalzing
OBJECTIVE: Up to one third of patients with T-cell large granular lymphocyte leukemia (T-LGL-leukemia) display symptoms of rheumatoid arthritis (RA). In Crohn's disease and in psoriasis treatment with TNFα-inhibitors is associated with hepatosplenic γδT-cell-lymphoma and with clonal expansion of γδT-cells, respectively. Here, we determine the prevalence of clonal T-LGL cells in patients with RA and define risk factors for this rare hematologic malignancy. METHODS: 529 RA-patients were recruited between November, 2013 and August, 2015...
June 25, 2018: Arthritis & Rheumatology
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
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
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
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
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
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]
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
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...
June 26, 2018: International Immunology
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
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
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
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
Remo C Russo, Benedetta Savino, Massimiliano Mirolo, Chiara Buracchi, Giovanni Germano, Achille Anselmo, Luca Zammataro, Fabio Pasqualini, Alberto Mantovani, Massimo Locati, Mauro M Teixeira
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 the levels of inflammatory CC chemokines. The role of ACKR2 in fibrogenesis is unknown. The purpose of the study was to investigate the role of ACKR2 in the context of pulmonary fibrosis. 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...
June 1, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
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
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