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https://www.readbyqxmd.com/read/29222435/long-term-maintenance-of-peripheral-blood-derived-human-nk-cells-in-a-novel-human-il-15-transgenic-nog-mouse
#1
Ikumi Katano, Chiyoko Nishime, Ryoji Ito, Tsutomu Kamisako, Takuma Mizusawa, Yuyo Ka, Tomoyuki Ogura, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
We generated a novel mouse strain expressing transgenic human interleukin-15 (IL-15) using the severe immunodeficient NOD/Shi-scid-IL-2Rγ null (NOG) mouse genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from the peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. In addition, the cell number increased, and the hu-PB-NK cells persisted for 3 months without signs of xenogeneic graft versus host diseases (xGVHD). These in vivo-expanded hu-PB-NK cells maintained the original expression patterns of various surface antigens, including NK receptors and killer cell immunoglobulin-like receptor (KIR) molecules...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29217299/high-pd-l1-cd86-mfi-ratio-and-il-10-secretion-characterize-human-regulatory-dendritic-cells-generated-for-clinical-testing-in-organ-transplantation
#2
Alan F Zahorchak, Camila Macedo, David E Hamm, Lisa H Butterfield, Diana M Metes, Angus W Thomson
Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression...
September 14, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29216683/human-perforin-gene-variation-is-geographically-distributed
#3
Robin C Willenbring, Yasuhiro Ikeda, Larry R Pease, Aaron J Johnson
BACKGROUND: Deleterious mutations in PRF1 result in lethal, childhood disease, familial hemophagocytic lymphohistiocytosis type 2 (FHL 2). However, not all mutations in PRF1 are deleterious and result in FHL 2. Currently, these nondeleterious mutations are being investigated in the onset of numerous disorders, such as lymphomas and diabetes. Yet, there is still an overwhelmingly large amount of PRF1 mutations that are not associated with disease. METHODS: We conducted a post hoc analysis of the PRF1 mutations in the coding region using the recently published Exome Aggregation Consortium genomes, Leiden Open Variation Database, NCBI SNP database, and primary literature to better understand PRF1 variation in the human population...
December 7, 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/29201936/targeted-cell-to-cell-delivery-of-protein-payloads-via-the-granzyme-perforin-pathway
#4
Daniel J Woodsworth, Lisa Dreolini, Libin Abraham, Robert A Holt
There is great potential for engineering cellular therapeutics by repurposing biological systems. Here, we report utilization of the granzyme-perforin pathway of cytotoxic lymphocytes as a cell-to-cell protein delivery module. We designed and constructed granzyme B-derived chaperone molecules fused to a fluorescent protein payload and expressed these constructs in natural killer (NK) cells. Using confocal microscopy and flow cytometry, we investigated the co-localization of the chaperones with lytic granules and the chaperone-mediated transfer of the fluorescent protein payload from NK to target cells in co-culture experiments...
December 15, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29194614/immunomodulatory-effects-of-foreskin-mesenchymal-stromal-cells-fsk-mscs-on-natural-killer-nk-cells
#5
Mehdi Najar, Mohammad Fayyad-Kazan, Nathalie Meuleman, Dominique Bron, Hussein Fayyad-Kazan, Laurence Lagneaux
Foreskin-mesenchymal stromal cells (FSK-MSCs) are immune-privileged thus making them valuable immunotherapeutic cell product. Characterization of the relationship between FSK-MSCs and natural killer (NK) cells is essential to improve cell-based therapy. In the present study, we studied for the first time FSK-MSCs-NK interaction and showed that the result of such cross talk was robustly dependent on the type of cytokines (IL-2, IL-12, IL-15 and IL-21) employed to activate NK cells. Distinctly activated-NK cells showed uneven cytotoxicity against FSK-MSCs, triggering their death in fine...
December 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29182664/differential-inhibitory-and-activating-nk-cell-receptor-levels-and-nk-nkt-like-cell-functionality-in-chronic-and-recovered-stages-of-chikungunya
#6
Subrat Thanapati, Mohini A Ganu, Anuradha S Tripathy
The role of natural killer (NK; CD3-CD56+)/NKT (CD3+CD56+)-like cells in chikungunya virus (CHIKV) disease progression/recovery remains unclear. Here, we investigated the expression profiles and function of NK and NKT-like cells from 35 chronic chikungunya patients, 30 recovered individuals, and 69 controls. Percentage of NKT-like cells was low in chronic chikungunya patients. NKp30+, CD244+, DNAM-1+, and NKG2D+ NK cell percentages were also lower (MFI and/or percentage), while those of CD94+ and NKG2A+ NKT-like cells were higher (MFI and/or percentage) in chronic patients than in recovered subjects...
2017: PloS One
https://www.readbyqxmd.com/read/29174982/cd4-t-cell-mediated-cytotoxicity-is-associated-with-mhc-class-ii-expression-on-malignant-cd19-b-cells-in-diffuse-large-b-cell-lymphoma
#7
Yong Zhou, Jie Zha, Zhijuan Lin, Zhihong Fang, Hanyan Zeng, Jintao Zhao, Yiming Luo, Zhifeng Li, Bing Xu
Diffuse large B cell lymphoma (DLBCL) is a common B cell malignancy with approximately 30% of patients present relapsed or refractory disease after first-line therapy. Research of further treatment options is needed. Cytotoxic CD4+ T cells express cytolytic molecules and have potential antitumor function. Here, we showed that the CD19+ cells from DLBCL patients presented significantly reduced expression of MHC II molecules than those from healthy controls. Three years after the first-line treatment, patients that presented relapsed disease had significantly lower MHC II expression on their CD19+ cells than patients who did not show recurrence...
November 22, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29165150/search-for-biomarkers-of-asbestos-exposure-and-asbestos-induced-cancers-in-investigations-of-the-immunological-effects-of-asbestos
#8
REVIEW
Hidenori Matsuzaki, Naoko Kumagai-Takei, Suni Lee, Megumi Maeda, Nagisa Sada, Tamayo Hatayama, Shoko Yamamoto, Miho Ikeda, Kei Yoshitome, Yu Min, Yasumitsu Nishimura, Takemi Otsuki
The immunological effects of asbestos exposure on various lymphocytes such as the regulatory T cell (Treg), responder CD4+ T helper cell (Tresp), CD8+ cytotoxic T lymphocytes (CTL), and natural killer (NK) cells were investigated. Results show that asbestos exposure impairs antitumor immunity through enhancement of regulatory T cell function and volume, reduction of CXCR3 chemokine receptor in responder CD4+ T helper cells, and impairment of the killing activities of CD8+ cytotoxic T lymphocytes (CTL) and NK cells...
June 9, 2017: Environmental Health and Preventive Medicine
https://www.readbyqxmd.com/read/29163816/sestrin2-and-sestrin3-suppress-nk-92-cell-mediated-cytotoxic-activity-on-ovarian-cancer-cells-through-ampk-and-mtorc1-signaling
#9
Xuejin Wang, Weifeng Liu, Deyi Zhuang, Shaoxian Hong, Jingfang Chen
Ovarian cancer is one of the major cancer types. NK-92 cell line, which has consistently and reproducibly high anti-tumor cytotoxicity, may be used for immunotherapy against ovarian cancer. Understanding the mechanisms that regulate the anti-tumor activity of NK-92 cells is important for developing novel therapeutic strategies. In the current study, using an ovarian cancer xenograft mouse model, we identified the up-regulation of sestrin2 (SESN2) and sestrin3 (SESN3) in intratumoral NK-92 cells. Lentivirus-transduced NK-92 cells, which overexpressed SESN2 or SESN3 after doxycycline treatment, exhibited less expression of activating receptors, perforin and granzyme B...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163540/local-high-dose-radiotherapy-induces-systemic-immunomodulating-effects-of-potential-therapeutic-relevance-in-oligometastatic-breast-cancer
#10
Elena Muraro, Carlo Furlan, Michele Avanzo, Debora Martorelli, Elisa Comaro, Aurora Rizzo, Damiana A Fae', Massimiliano Berretta, Loredana Militello, Alessandro Del Conte, Simon Spazzapan, Riccardo Dolcetti, Marco Trovo'
Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC) patients, the use of stereotactic body radiotherapy (SBRT) favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs), improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to "switch on" the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158781/hypothalamic-beta-endorphin-neurons-suppress-preneoplastic-and-neoplastic-lesions-development-in-1-2-dimethylhydrazine-induced-rat-colon-cancer-model
#11
Sengottuvelan Murugan, Yatee Dave, Ankush Rakhit, Dipak K Sarkar
In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29157909/sulfated-fucan-from-sea-cucumber-stichopus-japonicus-on-nk-cell-activation-and-cytotoxicity
#12
Utoomporn Surayot, SangMin Lee, SangGuan You
The aqueous crude sulfated fucan (SF) from Stichopus japonicus was extracted and fractionated using anion-exchange chromatography to obtain four fractions (F1, F2, F3 and F4) and to investigate their NK cell activation and cytotoxicity. The most potent NK cell cytotoxicity (45% at 250μg/mL) against HeLa cells was observed by F1 treatment, on the other hand, F3 and F4 treatment exhibited strong NK cell cytotoxicity (31-34% at 250μg/mL) against HepG2 and HT-29 cells. The SF treatment enhanced the activation of NK cells through the mRNA expression of INF-γ, an activating receptor (NKp30), lysing proteins (perforin and granzyme-B) as well as a death ligand (FasL)...
November 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29145176/the-membrane-attack-complex-perforin-superfamily
#13
Gabriel Moreno-Hagelsieb, Bennett Vitug, Arturo Medrano-Soto, Milton H Saier
The membrane attack complex/perforin (MACPF) superfamily consists of a diverse group of proteins involved in bacterial pathogenesis and sporulation as well as eukaryotic immunity, embryonic development, neural migration and fruiting body formation. The present work shows that the evolutionary relationships between the members of the superfamily, previously suggested by comparison of their tertiary structures, can also be supported by analyses of their primary structures. The superfamily includes the MACPF family (TC 1...
November 17, 2017: Journal of Molecular Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29141887/apoptosis-in-mesenchymal-stromal-cells-induces-in-vivo-recipient-mediated-immunomodulation
#14
Antonio Galleu, Yanira Riffo-Vasquez, Cristina Trento, Cara Lomas, Luigi Dolcetti, Tik Shing Cheung, Malte von Bonin, Laura Barbieri, Krishma Halai, Sophie Ward, Ling Weng, Ronjon Chakraverty, Giovanna Lombardi, Fiona M Watt, Kim Orchard, David I Marks, Jane Apperley, Martin Bornhauser, Henning Walczak, Clare Bennett, Francesco Dazzi
The immunosuppressive activity of mesenchymal stromal cells (MSCs) is well documented. However, the therapeutic benefit is completely unpredictable, thus raising concerns about MSC efficacy. One of the affecting factors is the unresolved conundrum that, despite being immunosuppressive, MSCs are undetectable after administration. Therefore, understanding the fate of infused MSCs could help predict clinical responses. Using a murine model of graft-versus-host disease (GvHD), we demonstrate that MSCs are actively induced to undergo perforin-dependent apoptosis by recipient cytotoxic cells and that this process is essential to initiate MSC-induced immunosuppression...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29138867/effect-of-xanthohumol-on-th1-th2-balance-in-a-breast-cancer-mouse-model
#15
Wenchao Zhang, Yanlong Pan, Panhong Gou, Cheng Zhou, Lianqing Ma, Qiming Liu, Yuping Du, Jinbo Yang, Qin Wang
Xanthohumol (XN), a prenylflavonoid found in the hop plant, Humulus lupulus, exhibits a variety of biological activities. Numerous studies have reported that XN inhibits the growth of many types of cancer cells, but the effects of XN on tumor immunity have not yet been studied. We explored the effect of XN on Th1/Th2 balance and the underlying mechanism based on a BALB/c-4T1 breast cancer mouse model. The results showed that XN significantly slowed down tumor growth and inhibited expression of antitumor proliferation protein Ki-67 as well as breast cancer-specific marker cancer antigen 15-3 (CA15-3)...
November 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29138222/decitabine-enhances-targeting-of-aml-cells-by-cd34-progenitor-derived-nk-cells-in-nod-scid-il2rgnull-mice
#16
Jeannette Cany, Mieke W H Roeven, Janneke S Hoogstad-van Evert, Willemijn Hobo, Frans Maas, Rosalia Franco Fernandez, Nicole M A Blijlevens, Walter J van der Velden, Gerwin Huls, Joop H Jansen, Nicolaas P M Schaap, Harry Dolstra
Combining NK cell adoptive transfer with hypomethylating agents (HMA) is an attractive therapeutic approach for patients with acute myeloid leukemia (AML). However, data regarding the impact of HMA on NK cell functionality are mostly derived from in vitro studies with high non-clinical relevant drug concentrations. Here, we report a comparative study of azacitidine and decitabine in combination with allogeneic NK cells generated from CD34+ hematopoietic stem and progenitor cells (HSPC-NK cells) in in vitro and in vivo AML models...
November 14, 2017: Blood
https://www.readbyqxmd.com/read/29130799/allergen-immunotherapy-modulates-sensitivity-of-treg-cells-to-apoptosis-in-a-rat-model-of-allergic-asthma
#17
Ankur Datta, Saibal Moitra, Prasanta K Das, Somnath Mondal, Sk Md Omar Faruk, Iman Hazra, Santanu K Tripathi, Swapna Chaudhuri
AIM: To study the apoptosis of Foxp3(+) Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. MATERIALS & METHODS: Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. RESULTS: Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy...
November 2017: Immunotherapy
https://www.readbyqxmd.com/read/29124751/detailed-characterization-of-human-mycobacterium-tuberculosis-specific-hla-e-restricted-cd8-t-cells
#18
Teresa Prezzemolo, Krista E van Meijgaarden, Kees Lmc Franken, Nadia Caccamo, Francesco Dieli, Tom Hm Ottenhoff, Simone A Joosten
HLA-E presented antigens are interesting targets for vaccination given HLA-Es' essentially monomorphic nature. We have shown previously that Mycobacterium tuberculosis (Mtb) peptides are presented by HLA-E to CD8(+) effector T-cells, but the precise phenotype and functional capacity of these cells remains poorly characterized. We have developed and utilized in this study a new protocol combining HLA-E tetramer with intracellular staining for cytokines, transcription factors and cytotoxic molecules to characterize these cells in depth...
November 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29122114/frequency-and-perforin-expression-of-different-lymphocyte-subpopulations-in-patients-with-lower-limb-fracture-and-thoracic-injury
#19
Nikola Grzalja, Tedi Cicvaric, Danijel Knezevic, Janja Kuharic, Alan Sustic, Bore Bakota, Simona Komen, Vlatka Sotosek Tokmadzic
INTRODUCTION: Trauma with multiple injuries is associated with a high risk of complications, which may be related to excessive stimulation of inflammatory and anti-inflammatory responses. Although the effects of polytrauma on the immune response have been well established at the cellular and molecular levels, there is little information about the changes in the cytolytic potential of immunocompetent cells, including expression of cytotoxic molecules such as perforin. Therefore, the objective of the present study was to analyse and compare differences in the frequency and perforin expression of leukocyte subpopulations in the peripheral blood of patients with lower limb fracture, thoracic injury, and simultaneous lower limb fracture and thoracic injury...
November 2017: Injury
https://www.readbyqxmd.com/read/29122079/sinonasal-t-cell-expression-of-cytotoxic-mediators-granzyme-b-and-perforin-is-reduced-in-patients-with-chronic-rhinosinusitis
#20
Sarah E Smith, Rodney J Schlosser, James R Yawn, Jose L Mattos, Zachary M Soler, Jennifer K Mulligan
BACKGROUND: CD8+ T cells and natural killer (NK) cells are cytotoxic cells that use granzyme B (GrB) and perforin. Defective cytotoxic function is known to play a role in dysregulated immune response as seen in chronic sinusitis, also referred to as chronic rhinosinusitis (CRS). However, to our knowledge, in the United States, neither GrB or perforin expression has been reported in patients with CRS. OBJECTIVE: The aim of this study was to investigate sinonasal cytotoxic cells, their mediators, and cell-specific distribution of these mediators in patients with CRS with nasal polyp (CRSwNP) and in patients with CRS without nasal polyp (CRSsNP)...
November 1, 2017: American Journal of Rhinology & Allergy
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