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Jordana Grazziela Coelho-Dos-Reis, Xiangming Li, Moriya Tsuji
The inability to elicit strong and durable cellular responses is a major obstacle in the development of successful vaccines, in particular those against malaria. In this regard, the generation of novel adjuvants that will potently boost cell-mediated immunity induced by candidate vaccines is helpful. We and others have found a glycolipid, called α-galactosylceramide (α-GalCer), which could be presented on CD1d expressed by antigen-presenting cells (APCs) and stimulate natural killer T (NKT) cells. This triggers the activation/maturation of APCs, particularly dendritic cells (DCs)...
2018: F1000Research
Jessica J O'Konek, Elena Ambrosino, Anja C Bloom, Lise Pasquet, Chandirasegaran Massilamany, Zheng Xia, Masaki Terabe, Jay A Berzofsky
A major advantage of immunotherapy of cancer is that effector cells induced at one site should be able to kill metastatic cancer cells in other sites or tissues. However, different tissues have unique immune components, and very little is known about whether effector T cells induced against tumors in one tissue can work against the same tumors in other tissues. Here, we used CT26 murine tumor models to investigate anti-tumor immune responses in the skin and lungs and characterized cross-protection between the two tissues...
2018: Oncoimmunology
Fatma Zehra Hapil, Gerhard Wingender
The surface of mammalian bodies is colonized by a multitude of microbial organisms, which under normal conditions support the host and are considered beneficial commensals. This requires, however, that the composition of the commensal microbiota is tightly controlled and regulated. The host immune system plays an important role in the maintenance of this microbiota composition. Here we focus on the contribution of one particular immune cell type, invariant Natural Killer (iNKT) cells, in this process. iNKT cells are a unique subset of T cells characterized by two main features...
June 12, 2018: Immunology
Francesca A Ververs, Eric Kalkhoven, Belinda Van't Land, Marianne Boes, Henk S Schipper
Invariant natural killer T (iNKT) cells are lipid-reactive T cells with profound immunomodulatory potential. They are unique in their restriction to lipid antigens presented in CD1d molecules, which underlies their role in lipid-driven disorders such as obesity and atherosclerosis. In this review, we discuss the contribution of iNKT cell activation to immunometabolic disease, metabolic programming of lipid antigen presentation, and immunometabolic activation of iNKT cells. First, we outline the role of iNKT cells in immunometabolic disease...
2018: Frontiers in Immunology
Dharmendra Singh, Manisha Ghate, Sheela Godbole, Smita Kulkarni, Madhuri Thakar
Background: CD1d restricted invariant natural killer T (iNKT) cells are important in the activation and regulation of immune responses. Limited information is available regarding the functional role of iNKT cells in the human immunodeficiency virus (HIV) disease progression. Methodology: α-GalCer stimulated iNKT cells were characterized for their functionality in terms of cytokine production (IFN-γ, TNF-α, IL-2, IL-4, and IL-21) and CD107a expression in HIV-1 infected [23 long-term non progressors (LTNPs), 28 progressors, 18 patients before and after suppressive anti-retroviral treatment (ART)] along with 25 HIV-1 negative subjects using multicolor flow cytometry...
2018: Frontiers in Immunology
L Gao, Y Fan, Y Yang, R Xie, J Yang, Z Chen
OBJECTIVE: A preliminary investigation on the proliferation and cultivation process of natural killer T cells (NKT) was carried out. We provide reference data for future NKT-related research and development. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy people and were induced by α-galactosylceramide (α-GalCer). The phenotypic changes of the cells and the activation and apoptosis of Caspase-3 were recorded for 3-4 weeks. RESULTS: The proliferation of the NKT cells continued for approximately 3 weeks, and then apoptosis started to occur...
June 2018: Transplantation Proceedings
Éilis Dockry, Seónadh O'Leary, Laura E Gleeson, Judith Lyons, Joseph Keane, Steven G Gray, Derek G Doherty
Immunotherapies that target CD1d-restricted invariant NKT (iNKT) cells can prevent tumor growth in murine models but trials in humans have shown limited clinical efficacy. Here, we show that iNKT cells are depleted from blood and bronchial lavage samples from patients with non-small cell lung cancer (NSCLC) suggesting a role for these cells in immunity against NSCLC. We interrogated the Lung Cancer Explorer and Kaplan-Meier Plotter databases of NSCLC patients and found that pulmonary CD1d expression is reduced in patients with NSCLC and that low expression of CD1d mRNA is significantly associated with poor patient survival...
2018: Oncoimmunology
Shinsuke Inuki, Emi Kashiwabara, Natsumi Hirata, Junichiro Kishi, Etsuko Nabika, Yukari Fujimoto
Th2-biasing CD1d ligands are attractive potential candidates for adjuvants and therapeutic drugs. However, the number of potent ligands is limited, and their biasing mechanism remain unclear. We have identified a series of novel Th2-biasing CD1d glycolipid ligands based on modification of their lipid part. These have shown high binding affinities and efficient Th2 cytokine production. Importantly, the truncated acyl chain-containing variants still retain their binding affinities and agonistic activities, which can be associated with an "anchoring effect," i...
June 4, 2018: Angewandte Chemie
Xinqiang Hong, Tiangeng Dong, Tuo Yi, Jianwei Hu, Zhen Zhang, Shengli Lin, Weixin Niu
Objective: The aim of the present study was to investigate the effects of 5-fluorouracil (5-Fu) and oxaliplatin on the function and activation pathways of mouse dendritic cells (DCs), and to clarify whether 5-Fu/oxaliplatin combined with the CD1d-MC38/α-galactosylceramide (α-GC) tumor vaccine exhibits synergistic effects on the treatment of colon cancer in mice. Methods: The combination of the Toll like receptor (TLR) ligands and/or 5-Fu/oxaliplatin was added into myeloid-derived DCs in vitro culture...
April 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Rui Dou, Zhenya Hong, Xiaosheng Tan, Fenfen Hu, Yajie Ding, Wei Wang, Zhihui Liang, Rongrong Zhong, Xiongwen Wu, Xiufang Weng
The rapid antitumor cytokine production and direct cytotoxicity confer invariant NKT (iNKT) cells ideal candidates for cancer therapy. However, the therapeutic potential of iNKT cells in T-cell malignant diseases remains elusive, as antigen presentation by T cells (T-T presentation) has been suggested to induce hyporesponsiveness of iNKT cells. In this study, we found discrepancies in iNKT cell responses against two T cell-origin cell lines (Jurkat and Molt-4). Human iNKT cells exhibited more intensive cytotoxicity and less efficient cytokine production in response to Fas-bearing Jurkat cells than those to the Fas-negative tumor cells (Molt-4 and myeloid-derived K562)...
May 18, 2018: Molecular Immunology
Shankar S Iyer, Thomas Gensollen, Amit Gandhi, Sungwhan F Oh, Joana F Neves, Frederic Collin, Richard Lavin, Carme Serra, Jonathan Glickman, Punyanganie S A de Silva, R Balfour Sartor, Gurdyal Besra, Russell Hauser, Anthony Maxwell, Amadeu Llebaria, Richard S Blumberg
Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs)...
May 17, 2018: Cell
Kamel Laribi, Mustapha Alani, Catherine Truong, Alix Baugier de Materre
OBJECTIVE: Mature T-cell lymphomas are a heterogeneous group of T-cell malignancies with a poor outcome. The discovery of new molecular biomarkers has led to the emergence of new drugs in recent years that target various signaling pathways. METHOD: We examined all pertinent published patents through 2015 that analyzed novel methods for the diagnosis and treatment of T cell lymphoma, as well as related published and unpublished studies. Selection criteria were established before data collection...
May 16, 2018: Recent Patents on Anti-cancer Drug Discovery
Andrea J White, Beth Lucas, William E Jenkinson, Graham Anderson
Most αβ T cells that form in the thymus are generated during mainstream conventional thymocyte development and involve the generation and selection of a diverse αβ TCR repertoire that recognizes self-peptide/MHC complexes. Additionally, the thymus also supports the production of T cell subsets that express αβ TCRs but display unique developmental and functional features distinct from conventional αβ T cells. These include multiple lineages of CD1d-restricted invariant NKT (iNKT) cells that express an invariant αβ TCR, branch off from mainstream thymocytes at the CD4+ CD8+ stage, and are potent producers of polarizing cytokines...
May 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Randy R Brutkiewicz, Laura Yunes-Medina, Jianyun Liu
Many reviews on the CD1d/NKT cell axis focus on the ability of CD1d-restricted NKT cells to serve as effector cells in a variety of disorders, be they infectious diseases, cancer or autoimmunity. In contrast, here, we discuss the ways that viruses, bacteria and tumor cells can evade the CD1d/NKT cell axis. As a result, these disease states have a better chance to establish a foothold and potentially cause problems for the subsequent adaptive immune response, as the host tries to rid itself of infections or tumors...
May 3, 2018: Current Opinion in Immunology
Alexandra C Bolognese, Weng-Lang Yang, Laura W Hansen, Archna Sharma, Jeffrey M Nicastro, Gene F Coppa, Ping Wang
Sepsis is the third leading cause of death in the neonatal population, due to susceptibility to infection conferred by immaturity of both the innate and adaptive components of the immune system. Invariant natural killer T (iNKT) cells are specialized adaptive immune cells that possess important innate-like characteristics and have not yet been well-studied in septic neonates. We hypothesized that iNKT cells would play an important role in mediating the neonatal immune response to sepsis. To study this, we subjected 5- to 7-day-old neonatal C57BL/6 mice to sepsis by intraperitoneal (i...
2018: Frontiers in Immunology
Helena Migalovich Sheikhet, Jose Villacorta Hidalgo, Paul Fisch, Alexandra Balbir-Gurman, Yolanda Braun-Moscovici, Ilan Bank
Objectives: γδ T cells, a non-conventional innate lymphocyte subset containing cells that can be activated by lipids and phosphoantigens, are abnormally regulated in systemic sclerosis (SSc). To further evaluate the significance of this dysregulation, we compared how exposure to an autoantigenic lipid, cardiolipin (CL), during co-stimulation with an amino-bisphosphonate (zoledronate, zol), affects the activation and cytokine production of SSc and healthy control (HC) γδ T cells. Methods: Expression of CD25 on Vγ9+ , Vδ1+ , and total CD3+ T cells in cultured peripheral blood mononuclear cells (PBMCs), their binding of CD1d tetramers, and the effect of monoclonal antibody (mAb) blockade of CD1d were monitored by flow cytometry after 4 days of in vitro culture...
2018: Frontiers in Immunology
Ashanty M Melo, Lei Zhang, Éilis F Dockry, Andreea Petrasca, Yasmeen G Ghnewa, Eamon P Breen, Maria E Morrissey, Ciara O'Reilly, Robyn Bruen, Andrew O'Meara, Joanne Lysaght, Xiangming Zhu, Derek G Doherty
Invariant natural killer T (iNKT) cells recognize glycolipid antigens bound to CD1d molecules on antigen-presenting cells. Therapeutic activation of iNKT cells with the xenogeneic glycolipid α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in murine models, but clinical trials using α-GalCer-stimulated human iNKT cells have shown limited efficacy. We synthesized a series of thioglycoside analogs of α-GalCer with different substituents to the galactose residue and found that two of these compounds, XZ7 and XZ11, bound to CD1d-transfected HeLa cells and activated lines of expanded human iNKT cells...
April 6, 2018: Glycobiology
Payal Mandal, Prachi Tewari, Sachin Kumar, Sarika Yadav, Anjaneya Ayanur, Rajnish K Chaturvedi, Mukul Das, Anurag Tripathi
Consumption of edible oils contaminated with Argemone oil (AO) leads to a clinical condition called "Epidemic dropsy". Earlier studies have reported that metabolism and oxidative stress primarily contributes to AO toxicity, however, the involvement of immune system has not been assessed so far. Therefore, the present study was undertaken to systematically assess the effect of AO exposure on the function of immune system in Balb/c mice. The repeated exposure of AO for 28 days caused prominent regression of spleen and thymus; severe inflammatory changes in spleen depicted by the loss of distinct follicles, increased megakaryocyte infiltration, and enhanced expression levels of inflammatory markers (iNOS & COX-2)...
May 1, 2018: Chemico-biological Interactions
Xiaosheng Tan, Yajie Ding, Peng Zhu, Rui Dou, Zhihui Liang, Daofeng Yang, Zhiyong Huang, Wei Wang, Xiongwen Wu, Xiufang Weng
Activation of invariant NKT (iNKT) cells manifests antiviral immune responses in vivo. However, clinical trials have failed to show consistent hepatitis B virus (HBV) DNA reduction postadministration of iNKT cell-specific agonist α-galactosylceramide (α-GalCer). In this study, we aimed to investigate HBV infection-related iNKT cell defects and explore iNKT cell-based therapeutic potential for chronic hepatitis B (CHB). Liver specimens from 30 HBV-infected hepatocellular carcinoma patients were collected for CD1d/hepatitis B surface Ag (HBsAg) staining and/or intrahepatic iNKT cell assay...
May 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Shasha Zhu, Huimin Zhang, Li Bai
Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma...
June 2018: Frontiers of Medicine
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