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https://www.readbyqxmd.com/read/29769244/a-cs1-nkg2d-bispecific-antibody-collectively-activates-cytolytic-immune-cells-against-multiple-myeloma
#1
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
https://www.readbyqxmd.com/read/29740438/the-nkg2d-nkg2dl-axis-in-the-crosstalk-between-lymphoid-and-myeloid-cells-in-health-and-disease
#2
REVIEW
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
https://www.readbyqxmd.com/read/29735644/invariant-nkt-cells-and-control-of-the-thymus-medulla
#3
REVIEW
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
https://www.readbyqxmd.com/read/29734045/immune-evasion-of-the-cd1d-nkt-cell-axis
#4
REVIEW
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
https://www.readbyqxmd.com/read/29731751/unique-action-of-interleukin-18-on-t-cells-and-other-immune-cells
#5
REVIEW
Kenji Nakanishi
Interleukin (IL)-18 was originally discovered as a factor that enhances interferon (IFN)-γ production by anti-CD3-stimulated Th1 cells, particularly in association with IL-12. IL-12 is a cytokine that induces development of Th1 cells. IL-18 cannot induce Th1 cell development, but has the capacity to activate established Th1 cells to produce IFN-γ in the presence of IL-12. Thus, IL-18 is regarded as a proinflammatory cytokine that facilitates type 1 responses. However, in the absence of IL-12 but presence of IL-2, IL-18 stimulates natural killer cells, NKT cells, and even established Th1 cells to produce IL-3, IL-9, and IL-13...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29728401/immune-regulatory-cell-infusion-for-graft-versus-host-disease-prevention-and-therapy
#6
Bruce R Blazar, Kelli P A MacDonald, Geoffrey R Hill
Current approaches to prevent and treat graft-versus-host disease (GVHD) after stem cell transplantation rely principally on pharmacological immune suppression. Such approaches are limited by drug toxicity, non-specific immune suppression and a requirement for long-term therapy. Our increased understanding of the regulatory cells and molecular pathways involved in limiting pathogenic immune responses opens the opportunity for the use of these cell subsets to prevent and/or GVHD. The theoretical advantages of this approach is permanency of effect, potential for facilitating tissue repair, and induction of tolerance that obviates a need for ongoing drug therapy...
May 4, 2018: Blood
https://www.readbyqxmd.com/read/29727769/lymphocyte-and-monocyte-subpopulations-in-severe-aortic-stenosis-at-the-time-of-surgical-intervention
#7
Piotr Mazur, Aleksandra Mielimonka, Joanna Natorska, Ewa Wypasek, Bogusław Gawęda, Dorota Sobczyk, Przemysław Kapusta, Krzysztof Piotr Malinowski, Bogusław Kapelak
INTRODUCTION: Aortic stenosis (AS) is the most common acquired valvular heart disease in adults. Immune system involvement becomes evident during AS development. We sought to investigate the role of different circulating lymphocyte and monocyte subpopulations, with focus on CD4+ CD8+ and natural killer T (NKT) cells, in AS. MATERIAL AND METHODS: Blood samples and aortic valves were obtained from patients undergoing elective aortic valve surgery. Valves were dissected and underwent genetic analyses and calcium content assessment...
April 7, 2018: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/29705247/transfer-of-gene-corrected-t-cells-corrects-humoral-and-cytotoxic-defects-in-x-linked-lymphoproliferative-disease-xlp1
#8
Neelam Panchal, Ben Houghton, Begona Diez, Sujal Ghosh, Ida Ricciardelli, Adrian J Thrasher, H Bobby Gaspar, Claire Booth
BACKGROUND: XLP1 arises from mutations in the SH2D1A gene encoding SAP, an adaptor protein expressed in T, NK and NKT cells. Defects lead to abnormalities of T and NK cell cytotoxicity and T cell dependent humoral function. Clinical manifestations include haemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinaemia. Curative treatment is limited to haematopoietic stem cell transplant with outcome reliant on a good donor match. OBJECTIVES: As most symptoms arise from defective T cell function, we investigated whether transfer of SAP gene corrected T cells could reconstitute known effector cell defects...
April 26, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29686681/-anaplasma-phagocytophilum-related-defects-in-cd8-nkt-and-nk-lymphocyte-cytotoxicity
#9
Diana G Scorpio, Kyoung-Seong Choi, J Stephen Dumler
Human granulocytic anaplasmosis, caused by the tick-transmitted Anaplasma phagocytophilum , is not controlled by innate immunity, and induces a proinflammatory disease state with innate immune cell activation. In A. phagocytophilum murine infection models, hepatic injury occurs with production of IFNγ thought to be derived from NK, NKT cells, and CD8 T lymphocytes. Specific A. phagocytophilum ligands that drive inflammation and disease are not known, but suggest a clinical and pathophysiologic basis strikingly like macrophage activation syndrome (MAS) and hemophagocytic syndrome (HPS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29684201/dysregulation-of-epstein-barr-virus-infection-in-hypomorphic-zap70-mutation
#10
Akihiro Hoshino, Takehiro Takashima, Kenichi Yoshida, Akira Morimoto, Yuta Kawahara, Tzu-Wen Yeh, Tsubasa Okano, Motoi Yamashita, Noriko Mitsuiki, Kohsuke Imai, Takashi Sakatani, Atsuko Nakazawa, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Tomohiro Morio, Hirokazu Kanegane
Background: Some patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes. Methods: We sought to describe the clinical and immunologic phenotype of a 21-month-old boy having EBV-associated LPD who was in good health till then. A genetic and immunologic analysis was performed...
April 19, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29680372/inkt-cells-ameliorate-human-autoimmunity-lessons-from-alopecia-areata
#11
Amal Ghraieb, Aviad Keren, Alex Ginzburg, Yehuda Ullmann, Adam G Schrum, Ralf Paus, Amos Gilhar
Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10...
April 18, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29679611/control-of-t-cell-effector-functions-by-mirnas
#12
Daniel P Inácio, Tiago Amado, Bruno Silva-Santos, Anita Q Gomes
The differentiation of effector T cells is a tightly regulated process that relies on the selective expression of lineage-defining master regulators that orchestrate unique transcriptional programs, including the production of distinct sets of effector cytokines. miRNAs are post-transcriptional regulators that are now viewed as critical players in these gene expression networks and help defining cell identity and function. This review summarises the role of individual miRNAs in the regulation of the differentiation of effector T cell subsets, including CD4+ T helper cells, cytotoxic CD8+ T cells and innate-like NKT cells...
April 18, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29679490/increased-nk-cell-subsets-with-inhibitory-cytokines-and-inhibitory-surface-receptors-in-patients-with-recurrent-miscarriage-and-decreased-or-normal-subsets-in-kidney-transplant-recipients-late-post-transplant
#13
Li Zhu, Mostafa Aly, Haihao Wang, Hristos Karakizlis, Rolf Weimer, Christian Morath, Ruben Jeremias Kuon, Bettina Toth, Naruemol Ekpoom, Gerhard Opelz, Volker Daniel
BACKGROUND: Patients with recurrent miscarriage (RM) show up-regulated cytotoxic NK cells that are suspected to play a causal role in abortion. In the present study, we investigated counter-regulating inhibitory mechanisms and compared the results in RM patients with those of healthy controls (HC), patients with end stage renal disease (ESRD) and kidney transplant recipients late post-transplant (TX). METHODS: NK, NKT and T cell subsets were analyzed in the peripheral blood of 31 RM, 14 female ESRD and 9 female TX patients as well as 21 female HC using eight-color fluorescence flow cytometry...
April 21, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29677387/il13r%C3%AE-2-expression-identifies-tissue-resident-il-22-producing-plzf-innate-t-cells-in-the-human-liver
#14
Dominic Paquin-Proulx, Benjamin C Greenspun, Lise Pasquet, Benedikt Strunz, Soo Aleman, Karolin Falconer, Masaki Terabe, Jay A Berzofsky, Johan K Sandberg, Espen Melum, Douglas F Nixon, Niklas K Björkström
Innate lymphocytes are selectively enriched in the liver where they have important roles in liver immunology. Murine studies have shown that type I NKT cells can promote liver inflammation whereas type II NKT cells have an anti-inflammatory role. In humans, type II NKT cells were found to accumulate in the gut during inflammation and IL13Rα2 was proposed as a marker for these cells. In the human liver, less is known about type I and II NKT cells. Here, we studied the phenotype and function of human liver T cells expressing IL13Rα2...
April 20, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29665972/intranasal-delivery-of-influenza-antigen-by-nanoparticles-but-not-nkt-cell-adjuvant-differentially-induces-the-expression-of-b-cell-activation-factors-in-mice-and-swine
#15
Sankar Renu, Santosh Dhakal, Eunsoo Kim, Jonathan Goodman, Yashavanth S Lakshmanappa, Michael J Wannemuehler, Balaji Narasimhan, Prosper N Boyaka, Gourapura J Renukaradhya
Intranasal vaccination of pigs with poly lactic-co-glycolic acid and polyanhydride nanoparticles delivered inactivated influenza virus provides cross-reactive T-cell response, but not antibody response, resulting in incomplete protection and no reduction in nasal virus shedding. Expression of BAFF and Th2 transcription factor GATA-3 were downregulated in lungs of pigs vaccinated with influenza nanovaccine, but in mice it upregulated the expression of BAFF and cytokine TGFβ in cervical lymph nodes. However, the intranasal iNKT cell adjuvant, α-Galctosylceramide upregulates the expression of BAFF in pig lungs...
April 11, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29664401/histone-deacetylase-7-mediates-tissue-specific-autoimmunity-via-control-of-innate-effector-function-in-invariant-natural-killer-t-cells
#16
Herbert G Kasler, Intelly S Lee, Hyung W Lim, Eric Verdin
We report that Histone Deacetylase 7 (HDAC7) controls the thymic effector programming of Natural Killer T (NKT) cells, and that interference with this function contributes to tissue-specific autoimmunity. Gain of HDAC7 function in thymocytes blocks both negative selection and NKT development, and diverts Vα14/Jα18 TCR transgenic thymocytes into a Tconv-like lineage. Conversely, HDAC7 deletion promotes thymocyte apoptosis and causes expansion of innate-effector cells. Investigating the mechanisms involved, we found that HDAC7 binds PLZF and modulates PLZF-dependent transcription...
April 17, 2018: ELife
https://www.readbyqxmd.com/read/29643992/description-of-organ-specific-phenotype-and-functional-characteristics-of-tissue-resident-lymphocytes-from-liver-transplantation-donor-and-research-on-immune-tolerance-mechanism-of-liver
#17
Yunpeng Shi, Ping Zhang, Guangyi Wang, Xingkai Liu, Xiaodong Sun, Xin Zhang, Haijun Li, Jun Qi, Lei Ding, Ting Li, Ruoyan Zhang, Yuguo Chen, Jianpeng Zhou, Guoyue Lv, Zhengkun Tu
Aim: Prior to transplantation, Donation after Cardiac Death (DCD) liver transplantation livers are perfused with preservation solution. Therefore, this provides an abundant source of human liver lymphocytes, as well as mesenteric lymph node and spleen for the study of lymphocyte subset diversity in the peripheral blood, lymph node, spleen and liver. Methods: Lymphocyte subsets were isolated and purified from peripheral blood, lymph node, spleen and liver perfusion, the phenotypic and functional analysis of the tissue resident lymphocyte were performed by flow cytometry...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643189/elevated-hepatic-cd1d-levels-coincide-with-invariant-nkt-cell-defects-in-chronic-hepatitis-b-virus-infection
#18
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...
April 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29623561/nkt-cells-in-liver-diseases
#19
REVIEW
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...
April 6, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29616022/temporal-regulation-of-natural-killer-t-cell-interferon-gamma-responses-by-%C3%AE-catenin-dependent-and-independent-wnt-signaling
#20
Jessica C Kling, Margaret A Jordan, Lauren A Pitt, Jana Meiners, Thao Thanh-Tran, Le Son Tran, Tam T K Nguyen, Deepak Mittal, Rehan Villani, Raymond J Steptoe, Kiarash Khosrotehrani, Stuart P Berzins, Alan G Baxter, Dale I Godfrey, Antje Blumenthal
Natural killer T (NKT) cells are prominent innate-like lymphocytes in the liver with critical roles in immune responses during infection, cancer, and autoimmunity. Interferon gamma (IFN-γ) and IL-4 are key cytokines rapidly produced by NKT cells upon recognition of glycolipid antigens presented by antigen-presenting cells (APCs). It has previously been reported that the transcriptional coactivator β-catenin regulates NKT cell differentiation and functionally biases NKT cell responses toward IL-4, at the expense of IFN-γ production...
2018: Frontiers in Immunology
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