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NKT cell

Maya E Kotas, Richard M Locksley
Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4+ T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense...
June 19, 2018: Immunity
Shin-Ichiro Fujii, Satoru Yamasaki, Yusuke Sato, Kanako Shimizu
Vaccines against a variety of infectious diseases have been developed and tested. Although there have been some notable successes, most are less than optimal or have failed outright. There has been discussion about whether either B cells or dendritic cells (DCs) could be useful for the development of antimicrobial vaccines with the production of high titers of antibodies. Invariant (i)NKT cells have direct antimicrobial effects as well as adjuvant activity, and iNKT-stimulated antigen-presenting cells (APCs) can determine the form of the ensuing humoral and cellular immune responses...
2018: Frontiers in Immunology
Duilio Pagano, Ester Badami, Pier Giulio Conaldi, Aurelio Seidita, Fabio Tuzzolino, Marco Barbàra, Fabrizio di Francesco, Alessandro Tropea, Rosa Liotta, Gaia Chiarello, Angelo Luca, Salvatore Gruttadauria
BACKGROUND: The ability to predict which recipients will successfully complete their posttransplant clinical course, is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates (LPs) could help identify risk factors portending adverse LT outcomes. METHODS: LPs were collected during the back-table surgical time after the procurement procedures for donors after brain death (DBDs)...
June 13, 2018: Transplantation
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
Bing Wei, Ran Zhang, Jingbo Zhai, Junfeng Zhu, Fangli Yang, Dan Yue, Xiaoyi Liu, Changlong Lu, Xun Sun
Background: Ganoderma lucidum polysaccharides (GLP) has anti-inflammatory and immunomodulatory effects. Dysregulated immune responses are involved in the pathogenesis of dextran sulfate sodium (DSS)-induced colitis. The aim of this study was to assess the therapeutic potential of GLP to alleviate DSS-induced colitis. Methods: The mice were administered with GLP by intragastric gavage daily for two weeks prior to the DSS treatment. Mice were orally administered with 2...
2018: Journal of Immunology Research
Victoria L DeVault, Murisa Malagic, Linda Mei, Oliver Dienz, Graham W J Lilley, Patrick Benoit, Somen K Mistri, Shawn C Musial, Jennifer L Ather, Matthew E Poynter, Jonathan E Boyson
Invariant NKT (iNKT) cells are tissue-resident innate-like T cells critical to the host immune response. We previously identified a 6.6 Mbp region on chromosome 1 as a major regulator of iNKT cell number and function in C57BL/6 and 129X1/SvJ mice. Here, we fine-mapped this locus by assessing the iNKT cell response to alpha-galactosylceramide (αGalCer) in a series of B6.129 congenic lines. This analysis revealed the presence of at least two genetic elements that regulate iNKT cell cytokine production in response to αGalCer...
June 8, 2018: Genes and Immunity
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
Jose Luis Rivas, Teresa Palencia, Guerau Fernández, Milagros García
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a pathological condition characterized by incapacitating fatigue and a combination of neurologic, immunologic, and endocrine symptoms. At present its diagnosis is based exclusively on clinical criteria. Several studies have described altered immunologic profiles; therefore, we proposed to further examine the more significant differences, particularly T and NK cell subpopulations that could be conditioned by viral infections, to discern their utility in improving the diagnosis and characterization of the patients...
2018: Frontiers in Immunology
Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H DeKruyff, Paul B Savag, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T Umetsu
BACKGROUND: Infection of suckling mice with influenza virus expands a CD4- CD8- double negative (DN) Natural Killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized and the underlying mechanisms of protection remain unknown. OBJECTIVE: We characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR...
May 28, 2018: Journal of Allergy and Clinical Immunology
Takahiro Uchida, Hiroyuki Nakashima, Akira Yamagata, Seigo Ito, Takuya Ishikiriyama, Masahiro Nakashima, Shuhji Seki, Hiroo Kumagai, Naoki Oshima
Lupus nephritis is a crucial complication of systemic lupus erythematosus. In this study, we investigated the roles of mouse natural killer T (NKT) cells in lupus nephritis. From 24 weeks of age, NZB/NZW F1 mice were injected with alpha-galactosylceramide (α-GalCer) or vehicle once a week for four weeks. In the α-GalCer group, the levels of proteinuria and blood urea nitrogen were significantly lower than those in the vehicle group. The histological evaluation showed a decrease in glomerular immune complex deposits and an alleviation of podocyte injury...
May 29, 2018: Scientific Reports
Sarita Kumari, Pushkar Shivam, Jagadish Hansa, Fauzia Jamal, Manish Kumar Singh, Sanjiva Bimal, Shyam Narayan, Krishna Pandey, Vidya Nand Ravi Das, Pradeep Das, Shubhankar K Singh
This study reports a structural and functional heterogeneity of CD8+ CD56+ NKT cells, which usually decrease quantitatively during visceral leishmaniasis. Based on fluorescence intensity of CD8 receptors on CD56+ NKT cells, two populations of CD8+ CD56+ NKT cells have been identified. These cells were recognized as CD8dim CD56+ NKT and CD8bright CD56+ NKT cells. We further analyzed the functional nature of CD8dim and CD8bright positive CD56+ NKT cells. In comparison to CD8bright CD56+ NKT cells, a significantly higher percentage of CD8dim CD56+ NKT cells expressed KIR during VL...
May 26, 2018: Human Immunology
Sarita Kumari, Pushkar Shivam, Shashank Kumar, Fauzia Jamal, Manish Kumar Singh, Sanjiva Bimal, Shyam Narayan, Krishna Pandey, Vidya Nand Ravi Das, Pradeep Das, Shubhankar K Singh
Sterile cure from visceralized Leishmania donovani (L. donovani) needs Th1 cell support along with the assistance from innate immune cells, NK cells and NKT cells. NKT cells play as a connecting link between innate and adaptive immune cell and support T helper cell function. Earlier, a categorical function of CD56 positive CD4+ or CD8+ NKT cells was reported in visceral leishmaniasis (VL). It was observed in in vitro that CD4+ CD56+ NKT cells, but not CD8+ CD56+ NKT cells, were accumulated at the L. donovani infection site...
May 25, 2018: Cytokine
Chen Chen, Wei Jiang, Zongjian Liu, Fengwu Li, Jian Yang, Yanlong Zhao, Yuanyuan Ran, Yan Meng, Xunming Ji, Xiaokun Geng, Huishan Du, Xiaoming Hu
BACKGROUND: Remote ischemic preconditioning (RIPC) of a limb has been reported to protect against ischemic stroke. Our previous results demonstrated that the RIPC-mediated neuroprotection is associated with alterations in circulating immune cell populations. Here, we evaluated the effect of the spleen, the largest reservoir of immune cells, on RIPC-mediated neuroprotection against stroke. METHODS: Noninvasive RIPC was achieved by four repeated cycles of 5-min blood flow constriction in the hindlimbs using a tourniquet...
May 28, 2018: Journal of Neuroinflammation
Chi Ma, Miaojun Han, Bernd Heinrich, Qiong Fu, Qianfei Zhang, Milan Sandhu, David Agdashian, Masaki Terabe, Jay A Berzofsky, Valerie Fako, Thomas Ritz, Thomas Longerich, Casey M Theriot, John A McCulloch, Soumen Roy, Wuxing Yuan, Vishal Thovarai, Shurjo K Sen, Mathuros Ruchirawat, Firouzeh Korangy, Xin Wei Wang, Giorgio Trinchieri, Tim F Greten
Primary liver tumors and liver metastasis currently represent the leading cause of cancer-related death. Commensal bacteria are important regulators of antitumor immunity, and although the liver is exposed to gut bacteria, their role in antitumor surveillance of liver tumors is poorly understood. We found that altering commensal gut bacteria in mice induced a liver-selective antitumor effect, with an increase of hepatic CXCR6+ natural killer T (NKT) cells and heightened interferon-γ production upon antigen stimulation...
May 25, 2018: Science
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
Wing Keung Chan, Siwen Kang, Youssef Youssef, Erin N Glankler, Emma R Barrett, Alex M Carter, Elshafa H Ahmed, Aman Prasad, Luxi Chen, Jianying Zhang, Don M Benson, Michael A Caligiuri, Jianhua Yu
Multiple myeloma (MM) is an incurable hematological malignancy of plasma cells with an estimated 30,000 new cases diagnosed each year in the United States, signifying the need for new therapeutic approaches. We hypothesized that targeting MM using a bispecific antibody (biAb) to simultaneously engage both innate and adaptive cytolytic immune cells could present potent antitumor activity. We engineered a biAb by fusing an anti-CS1 single chain variable fragment (scFv) and an anti-NKG2D scFv (CS1-NKG2D biAb)...
May 16, 2018: Cancer Immunology Research
Ana Stojanovic, Margareta P Correia, Adelheid Cerwenka
Natural killer group 2, member D (NKG2D) receptor is a type II transmembrane protein expressed by both innate and adaptive immune cells, including natural killer (NK) cells, CD8+ T cells, invariant NKT cells, γδ T cells, and some CD4+ T cells under certain pathological conditions. NKG2D is an activating NK receptor that induces cytotoxicity and production of cytokines by effector cells and supports their proliferation and survival upon engagement with its ligands. In both innate and T cell populations, NKG2D can costimulate responses induced by other receptors, such as TCR in T cells or NKp46 in NK cells...
2018: Frontiers in Immunology
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
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