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https://www.readbyqxmd.com/read/27907183/activation-of-innate-and-adaptive-immunity-by-a-recombinant-human-cytomegalovirus-strain-expressing-an-nkg2d-ligand
#1
Adriana Tomić, Pavankumar R Varanasi, Mijo Golemac, Suzana Malić, Peggy Riese, Eva M Borst, Eva Mischak-Weissinger, Carlos A Guzmán, Astrid Krmpotić, Stipan Jonjić, Martin Messerle
Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27905484/independent-control-of-natural-killer-cell-responsiveness-and-homeostasis-at-steady-state-by-cd11c-dendritic-cells
#2
Thuy Thanh Luu, Sridharan Ganesan, Arnika Kathleen Wagner, Dhifaf Sarhan, Stephan Meinke, Natalio Garbi, Günter Hämmerling, Evren Alici, Klas Kärre, Benedict J Chambers, Petter Höglund, Nadir Kadri
During infection and inflammation, dendritic cells (DC) provide priming signals for natural killer (NK) cells via mechanisms distinct from their antigen processing and presentation functions. The influence of DC on resting NK cells, i.e. at steady-state, is less well studied. We here demonstrate that as early as 1 day after DC depletion, NK cells in naïve mice downregulated the NKG2D receptor and showed decreased constitutive phosphorylation of AKT and mTOR. Subsequently, apoptotic NK cells appeared in the spleen concomitant with reduced NK cell numbers...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904959/differential-pulmonic-nk-and-nkt-cell-responses-in-schistosoma-japonicum-infected-mice
#3
Hefei Cha, Wenjuan Qin, Quan Yang, Hongyan Xie, Jiale Qu, Mei Wang, Daixiong Chen, Fang Wang, Nuo Dong, Longhua Chen, Jun Huang
Natural killer cells (NK cells) and natural killer T cells (NKT cells) play a role in anti-infection, anti-tumor, transplantation immunity, and autoimmune regulation. However, the role of NK and NKT cells during Schistosoma japonicum (S. japonicum) infection has not been widely reported, especially regarding lung infections. The aim of this study was to research the NK and NKT cell response to S. japonicum infection in the lungs of mice. Using immunofluorescent histological analysis, NK and NKT cells were found near pulmonary granulomas...
November 30, 2016: Parasitology Research
https://www.readbyqxmd.com/read/27903272/inhibition-of-bromodomain-and-extra-terminal-bet-proteins-increases-nkg2d-ligand-mica-expression-and-sensitivity-to-nk-cell-mediated-cytotoxicity-in-multiple-myeloma-cells-role-of-cmyc-irf4-mir-125b-interplay
#4
Maria Pia Abruzzese, Maria Teresa Bilotta, Cinzia Fionda, Alessandra Zingoni, Alessandra Soriani, Elisabetta Vulpis, Cristiana Borrelli, Beatrice Zitti, Maria Teresa Petrucci, Maria Rosaria Ricciardi, Rosa Molfetta, Rossella Paolini, Angela Santoni, Marco Cippitelli
BACKGROUND: Anti-cancer immune responses may contribute to the control of tumors after conventional chemotherapy, and different observations have indicated that chemotherapeutic agents can induce immune responses resulting in cancer cell death and immune-stimulatory side effects. Increasing experimental and clinical evidence highlight the importance of natural killer (NK) cells in immune responses toward multiple myeloma (MM), and combination therapies able to enhance the activity of NK cells against MM are showing promise in treating this hematologic cancer...
December 1, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27892653/low-baseline-levels-of-nk-cells-may-predict-a-positive-response-to-ipilimumab-in-melanoma-therapy
#5
Julia K Tietze, Daniela Angelova, Markus V Heppt, Thomas Ruzicka, Carola Berking
The introduction of immune checkpoint blockade (ICB) has been a breakthrough in the therapy of metastatic melanoma. The influence of ICB on T cell populations has been studied extensively but little is known about the effect on NK cells. In this study, we analysed the relative and absolute amounts of NK cells and of the subpopulations of CD56(dim) and CD56(bright) NK cells among the peripheral blood mononuclear cells (PBMCs) of 32 patients with metastatic melanoma before and under treatment with ipilimumab or pembrolizumab by flow cytometry...
November 28, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27884732/natural-killer-cell-subsets-and-receptor-expression-in-peripheral-blood-mononuclear-cells-of-a-healthy-korean-population-reference-range-influence-of-age-and-sex-and-correlation-between-nk-cell-receptors-and-cytotoxicity
#6
Minh-Trang Phan, Sejong Chun, Sun-Hee Kim, Alaa Kassim Ali, Seung-Hwan Lee, Seokho Kim, Soo-Hyun Kim, Duck Cho
BACKGROUND: The purpose of this study was to identify CD56(bright) and CD56(dim) natural killer (NK) cell subsets and analyze their receptors expression in a healthy Korean population, and to determine whether receptor expression correlates with age, sex, and cytotoxicity. MATERIALS AND METHODS: We performed multicolor flow cytometry assays to analyze the expression of various NK cell receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and NKp46) on both CD3(-)/CD56(dim) and CD3(-)/CD56(bright) NK cells in whole-blood samples from 122 healthy donors...
November 21, 2016: Human Immunology
https://www.readbyqxmd.com/read/27874833/a-herpesviral-induction-of-rae-1-nkg2d-ligand-expression-occurs-through-release-of-hdac-mediated-repression
#7
Trever T Greene, Maria Tokuyama, Giselle M Knudsen, Michele Kunz, James Lin, Alexander L Greninger, Victor R DeFilippis, Joseph L DeRisi, David H Raulet, Laurent Coscoy
Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands...
November 22, 2016: ELife
https://www.readbyqxmd.com/read/27869649/randomized-trial-of-calcipotriol-combined-with-5-fluorouracil-for-skin-cancer-precursor-immunotherapy
#8
Trevor J Cunningham, Mary Tabacchi, Jean-Pierre Eliane, Sara Moradi Tuchayi, Sindhu Manivasagam, Hengameh Mirzaalian, Ahu Turkoz, Raphael Kopan, Andras Schaffer, Arturo P Saavedra, Michael Wallendorf, Lynn A Cornelius, Shadmehr Demehri
BACKGROUND: Actinic keratosis is a precursor to cutaneous squamous cell carcinoma. Long treatment durations and severe side effects have limited the efficacy of current actinic keratosis treatments. Thymic stromal lymphopoietin (TSLP) is an epithelium-derived cytokine that induces a robust antitumor immunity in barrier-defective skin. Here, we investigated the efficacy of calcipotriol, a topical TSLP inducer, in combination with 5-fluorouracil (5-FU) as an immunotherapy for actinic keratosis...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27868339/fasl-and-the-nkg2d-receptor-are-required-for-the-secretion-of-the-tag7-pgrp-s-hsp70-complex-by-the-cytotoxic-cd8-lymphocytes
#9
Lidia P Sashchenko, Elena A Romanova, Olga K Ivanova, Tatiana N Sharapova, Denis V Yashin
Tag7 (PGRP-S or PGLYRP1), while possessing an antimicrobial activity, also exhibits an antitumor effect when in complex with the major heat shock protein Hsp70. The cytotoxic Tag7-Hsp70 complex is secreted by lymphocytes after interaction with the HLA-negative tumors. Previously, we have shown that IL-2 induces formation of the CD4(+) and CD8(+) cytotoxic subpopulations of human lymphocytes, which kill tumor cells through the FasL-Fas interaction. Here, we show that only the CD8(+) T cells are able to secrete the Tag7-Hsp70 complex...
November 20, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27862177/decreased-percentage-of-nkg2d-nk-cells-in-patients-with-incident-onset-of-type-1-diabetes
#10
Yupan Zhang, Haifeng Wang, Xiaoqian Lou, Xiaozhang Qu, Lichao Gao, Xiaolei Liu, Man Li, Hui Guo, Yanfang Jiang
Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency owing to autoimmune destruction of the pancreatic β cells. A significant decrease in NK cells in peripheral blood has been observed in patients with untreated T1DM. In the present study, we aimed to explore the role of NK cells and their subsets in young T1DM patients. A total of 30 children and adolescents with untreated T1DM and 27 healthy controls (HC) were recruited in this study. Flow cytometry analysis indicated that the percentage of peripheral blood CD3-CD56+ NK cells and NK cells subsets (CD56bright, CD56dim and CD56neg), were significantly decreased in the T1DM patients compared to healthy controls...
November 14, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27853638/natural-killer-cell-recognition-of-in-vivo-drug-induced-senescent-multiple-myeloma-cells
#11
Fabrizio Antonangeli, Alessandra Soriani, Biancamaria Ricci, Andrea Ponzetta, Giorgia Benigni, Stefania Morrone, Giovanni Bernardini, Angela Santoni
Recognition of tumor cells by the immune system is a key step in cancer eradication. Melphalan is an alkylating agent routinely used in the treatment of patients with multiple myeloma (MM), but at therapeutic doses it leads to an immunosuppressive state due to lymphopenia. Here, we used a mouse model of MM to investigate the ability of in vivo treatment with low doses of melphalan to modulate natural killer (NK) cell activity, which have been shown to play a major role in the control of MM growth. Melphalan treatment was able to enhance the surface expression of the stress-induced NKG2D ligands RAE-1 and MULT-1, and of the DNAM-1 ligand PVR (CD155) on MM cells, leading to better tumor cell recognition and killing by NK cells, as highlighted by NK cell increased degranulation triggered by melphalan-treated tumor cells...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27849169/mechanisms-of-acute-toxicity-in-nkg2d-chimeric-antigen-receptor-t-cell-treated-mice
#12
Marie-Louise Sentman, Joana M Murad, W James Cook, Ming-Ru Wu, Jake Reder, Susanne H Baumeister, Glenn Dranoff, Michael W Fanger, Charles L Sentman
Targeting cancer through the use of effector T cells bearing chimeric Ag receptors (CARs) leads to elimination of tumors in animals and patients, but recognition of normal cells or excessive activation can result in significant toxicity and even death. CAR T cells based on modified NKG2D receptors are effective against many types of tumors, and their efficacy is mediated through direct cytotoxicity and cytokine production. Under certain conditions, their ligands can be expressed on nontumor cells, so a better understanding of the potential off-tumor activity of these NKG2D CAR T cells is needed...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27834580/nkg2d-ligand-expression-in-pediatric-brain-tumors
#13
Kristen Haberthur, Kathryn Brennan, Virginia Hoglund, Stephanie Balcaitis, Harrison Chinn, Amira Davis, Shannon Kreuser, Conrad Winter, Sarah E S Leary, Gail H Deutsch, Richard G Ellenbogen, Courtney A Crane
Adult brain tumors establish an immunosuppressive tumor microenvironment as a modality of immune escape, with several immunotherapies designed to overcome this barrier. However, the relationship between tumor cells and immune cells in pediatric brain tumor patients is not as well-defined. In this study, we sought to determine whether the model of immune escape observed in adult brain tumors is reflected in patients with pediatric brain tumors by evaluating NKG2D ligand expression on tissue microarrays created from patients with a variety of childhood brain tumor diagnoses, and infiltration of Natural Killer and myeloid cells...
November 11, 2016: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27833611/activated-allogeneic-nk-cells-preferentially-kill-poor-prognosis-b-cell-chronic-lymphocytic-leukemia-cells
#14
Diego Sánchez-Martínez, Pilar M Lanuza, Natalia Gómez, Aura Muntasell, Elisa Cisneros, Manuela Moraru, Gemma Azaceta, Alberto Anel, Luis Martínez-Lostao, Martin Villalba, Luis Palomera, Carlos Vilches, José A García Marco, Julián Pardo
Mutational status of TP53 together with expression of wild-type (wt) IGHV represents the most widely accepted biomarkers, establishing a very poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) patients. Adoptive cell therapy using allogeneic HLA-mismatched Natural killer (NK) cells has emerged as an effective and safe alternative in the treatment of acute myeloid and lymphoid leukemias that do not respond to traditional therapies. We have described that allogeneic activated NK cells eliminate hematological cancer cell lines with multidrug resistance acquired by mutations in the apoptotic machinery...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27828717/natural-killer-group-2a-expressed-on-both-peripheral-cd3-cd56-nk-cells-and-cd3-cd8-t-cells-plays-a-pivotal-negative-regulatory-role-in-the-progression-of-hepatitis-b-virus-related-acute-on-chronic-liver-failure
#15
Rui-Tian Yi, Ying-Hua Niu, Hong-Li Liu, Tie-Ying Zhang, Yu-Cong Yang, Yu Zhang, Dong-Lin Yin, Tian-Yan Chen, Ying-Ren Zhao
To explore the role of surface receptors natural killer group 2A (NKG2A) and natural killer group 2D (NKG2D) on CD3(+)CD8(+)T cells and CD3(-)CD56(+)NK cells in the progression of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), we measured the expression of NKG2A and NKG2D on the surface of these 2 types of circulating cells by flow cytometry in 3 groups. One group consists of 36 patients with chronic hepatitis B (CHB), another one consists of 22 patients with HBV-related ACLF, and the last one has 12 normal controls (NC)...
November 9, 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27824136/lrba-is-essential-for-allogeneic-responses-in-bone-marrow-transplantation
#16
Mi Young Park, Raki Sudan, Neetu Srivastava, Sudha Neelam, Christie Youngs, Jia-Wang Wang, Robert W Engelman, William G Kerr
The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816971/the-anti-tumor-role-of-nk-cells-in-vivo-pre-activated-and-re-stimulated-by-interleukins-in-acute-lymphoblastic-leukemia
#17
Fengyan Jin, Hai Lin, Sujun Gao, Zheng Hu, Song Zuo, Liguang Sun, Chunhui Jin, Wei Li, Yanping Yang
Although natural killer cells (NK cells) were traditionally classified as members of the innate immune system, NK cells have recently been found also to be an important player in the adaptive immune systems. In this context, in vitro activation of NK cells by cytokines leads to generation of NK cells with memory-like properties characterized by increased interferon-γ (IFNγ) production. However, it remains to be defined whether these memory-like NK cells exist in vivo after cytokine activation. Furthermore, it is also unclear whether such memory-like NK cells induced in vivo by cytokines could have effective anti-leukemia response...
November 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815422/mucosal-and-systemic-%C3%AE-%C3%AE-t-cells-associated-with-control-of-simian-immunodeficiency-virus-infection
#18
Iskra Tuero, David Venzon, Marjorie Robert-Guroff
γδ T cells act as a first line of defense against invading pathogens. However, despite their abundance in mucosal tissue, little information is available about their functionality in this compartment in the context of HIV/SIV infection. In this study, we evaluated the frequency, phenotype, and functionality of Vδ1 and Vδ2 T cells from blood, rectum, and the female reproductive tract (FRT) of rhesus macaques to determine whether these cells contribute to control of SIV infection. No alteration in the peripheral Vδ1/Vδ2 ratio in SIV-infected macaques was observed...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27811019/matching-for-the-mica-129-polymorphism-is-beneficial-in-unrelated-hematopoietic-stem-cell-transplantation
#19
Daniel Fuerst, Christine Neuchel, Dietger Niederwieser, Donald Bunjes, Martin Gramatzki, Eva Wagner, Gerald Wulf, Bertram Glass, Michael Pfreundschuh, Hermann Einsele, Renate Arnold, Gernot Stuhler, Kerstin Schaefer-Eckart, Sebastian Freitag, Jochen Casper, Martin Kaufmann, Mohammed Wattad, Bernd Hertenstein, Stefan Klein, Mark Ringhoffer, Daphne Mytilineos, Chrysanthi Tsamadou, Carlheinz Mueller, Hubert Schrezenmeier, Joannis Mytilineos
MICA (MHC class I polypeptide-related sequence A) is a highly polymorphic ligand of the activating NKG2D receptor on NK-cells, γδ-T-cells and NKT-cells. MICA incompatibilities have been associated with an increased GvHD incidence and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA-matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n=1379), 9/10 (n=636) or 8/10 (n=157) HLA-alleles...
November 3, 2016: Blood
https://www.readbyqxmd.com/read/27801344/-the-significance-of-peripheral-blood-natural-killer-cell-surface-cd107a-nkg2d-and-serum-smica-in-patients-with-extranodal-nk-t-cell-lymphoma-nasal-type
#20
J X Liu, J W Wang, X Y Cui
The expression of CD107a, NKG2D on the surface of natural killer (NK) cells and serum soluble major histocompatibility complex class Ⅰ chain-related A (sMICA) level in patients with extranodal NK/T cell lymphoma, nasal type (ENKL) were detected.We found that CD107a expression was reduced on the surface of NK cells, suggesting impaired NK cell activity in ENKL patients, which may result from decreased NKG2D expression.
November 1, 2016: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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