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https://www.readbyqxmd.com/read/28418988/hiv-specific-cd8-t-cells-producing-ccl-4-are-associated-with-worse-immune-reconstitution-during-chronic-infection
#1
Rita Casetti, Carmela Pinnetti, Alessandra Sacchi, Gabriele De Simone, Veronica Bordoni, Eleonora Cimini, Nicola Tumino, Francesca Besi, Domenico Viola, Federica Turchi, Valentina Mazzotta, Andrea Antinori, Federico Martini, Adriana Ammassari, Chiara Agrati
BACKGROUND: Immunological non response represents the Achilles heel in the combination antiretroviral treatment (cART) effectiveness, and increases risk of clinical events and death. CD8 T cells play a crucial role in controlling HIV replication and polyfunctional HIV-specific CD8 T cells have been associated with non-progressive HIV infection. However, the possible role of polyfunctional CD8 T cells in predicting post-treatment immune reconstitution has not yet been explored. The aim of this study was to identify functional markers predictive of immunological response to cART in chronic HIV-infected patients...
April 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28388249/natural-killer-cell-subsets-and-their-functional-activity-in-beh%C3%A3-et-s-disease
#2
Fulya Cosan, Esin Aktas Cetin, Nilgun Akdeniz, Zeliha Emrence, Ayse Cefle, Gunnur Deniz
BACKGROUND: Behçet's disease (BD) is a rare, chronic autoinflammatory disorder of unknown origin. Natural killer (NK) cells are one of the major immunoregulatory cell groups of the innate immune system, but their role in BD pathogenesis is not well documented. OBJECTIVES: We aimed to investigate the role of NK cell subsets and their cytokine secretion and cytotoxic activity in patients with BD. PATIENTS AND METHODS: The study group consisted of BD patients who had only mucocutaneous involvement, and they were compared with healthy subjects...
April 7, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28383105/enhancement-of-cytokine-driven-nk-cell-ifn-%C3%AE-production-after-vaccination-of-hcmv-infected-africans
#3
Alansana Darboe, Ebrima Danso, Ed Clarke, Ama Umesi, Ebrima Touray, Rita Wegmuller, Sophie E Moore, Eleanor M Riley, Martin R Goodier
Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28373665/polyfunctional-natural-killer-cells-with-a-low-activation-profile-in-response-to-toll-like-receptor-3-activation-in-hiv-1-exposed-seronegative-subjects
#4
Josenilson F Lima, Luanda M S Oliveira, Nátalli Z Pereira, Alberto J S Duarte, Maria N Sato
Natural killer (NK) cells are the main mediator of the cytotoxic response in innate immunity and may be involved in resistance to HIV-1 infection in exposed seronegative (ESN) individuals. Toll-like receptor (TLR) signalling is crucial for NK cell activation. Here, we investigated the polyfunctional NK cell response to TLR3 activation in serodiscordant couples. ESN subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56(bright) and CD56(dim) cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28342224/interleukin-18-activates-vg9vd2-t-cells-from-hiv-individuals-recovering-the-response-to-phosphoantigen
#5
Alanna S Murday, Suchita Chaudhry, C David Pauza
OBJECTIVE: Identify an immunoregulatory factor that restores the phosphoantigen response of Vg9Vd2+ T cells from HIV+ individuals on antiretroviral therapy. DESIGN: Characterize the effects of IL-18 on proliferation and effector function in Vg9Vd2 T cells from HIV-negative individuals. Test whether exogenous IL-18 reconstitutes the Vg9Vd2 T cell response to phosphoantigen from HIV-positive donors. METHODS: The Vg9Vd2 T cells from HIV-negative individuals respond strongly to phosphoantigen or aminobisphosphonate stimulation of PBMC, while cells with similar T cell receptor profiles from HIV+ individuals only respond to aminobisphosphonate...
March 25, 2017: Immunology
https://www.readbyqxmd.com/read/28328926/frequency-and-role-of-nkp46-and-nkg2a-in-hepatitis-b-virus-infection
#6
Teppei Yoshioka, Tomohide Tatsumi, Takuya Miyagi, Kaori Mukai, Kumiko Nishio, Akira Nishio, Yoshinobu Yokoyama, Takahiro Suda, Tadashi Kegasawa, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Tetsuo Takehara
BACKGROUND AND AIM: Natural Killer (NK) cells are involved in the control of viral infection. However, the role of NK cells in chronic hepatitis B (CHB) remains unclear. This study investigated the frequencies and roles of NK cells in CHB, with a focus on activating receptor NKp46 and inhibitory receptor NKG2A. PATIENTS/METHOD: Peripheral blood lymphocytes were obtained from 71 CHB patients and 37 healthy subjects (HS). The expressions of NKp46 and NKG2A were analyzed using flow cytometry...
2017: PloS One
https://www.readbyqxmd.com/read/28317093/non-neutralizing-epitopes-induce-robust-hcv-specific-antibody-dependent-cd56-nk-cell-responses-in-chronic-hcv-infected-patients
#7
Lu Long, Manxue Jia, Xueying Fan, Hua Liang, Jiahua Wang, Liyan Zhu, Zhe Xie, Tao Shen
NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC) is of considerable interest in viral infection. However, little is known about NK-ADCC responses in chronic hepatitis C virus (HCV) infection. In this study, impaired nonspecific antibody-dependent CD56(+) NK cell responses were observed in chronic HCV infection, as shown by decreased degranulation (extracellular CD107a expression) and IFN-γ production in response to antibody-bound P815 cells. A peptide pool composed of epitopes recognized by anti-HCV-E1/E2 antibodies could induce pronounced HCV-specific antibody-dependent NK cell responses in sera from approximately half of the chronic HCV carriers...
March 20, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28306177/frequency-and-functional-characterization-of-exhausted-cd8-t-cells-in-chronic-lymphocytic-leukemia
#8
Saeid Taghiloo, Esmaeil Allahmoradi, Mohsen Tehrani, Hadi Hossein-Nataj, Ramin Shekarriz, Ghasem Janbabaei, Saeid Abediankenari, Hossein Asgarian-Omran
OBJECTIVES: The phenotypic and functional properties of Tim-3(+) /PD-1(+) /CD8(+) cells as exhausted T cells were investigated in chronic lymphocytic leukemia (CLL). METHODS: Frequency of CD8(+) /Tim-3(+) /PD-1(+) exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads-isolated CD8(+) T cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively...
March 17, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28281564/standardized-and-flexible-eight-colour-flow-cytometry-panels-harmonized-between-different-laboratories-to-study-human-nk-cell-phenotype-and-function
#9
John P Veluchamy, María Delso-Vallejo, Nina Kok, Fenna Bohme, Ruth Seggewiss-Bernhardt, Hans J van der Vliet, Tanja D de Gruijl, Volker Huppert, Jan Spanholtz
Advancements in multi-colour fluorescence activated cell sorting (FACS) panel warrant harmonized procedures to obtain comparable data between various laboratories. The intensifying clinical exploration of Natural Killer (NK) cell-based immunotherapy demands standardized and harmonized NK cell FACS panels and acquisition protocols. Eight colour FACS panels were designed to study human NK cell phenotype and function within peripheral blood mononuclear cells (PBMC). The panels were designed around fixed backbone markers and channels, covering antigens for non-NK lineage exclusion (CD3, TCRγδ, CD19, CD14, SYTOX(®) Blue) and NK cell selection (CD45, CD56, CD16), complemented with variable drop-in markers/channels to study NK cell phenotype (NKG2A, NKG2C, NKG2D and KIR2D) or NK cell function and activation (CD25, NKp44 and CD107a)...
March 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275109/intermittent-and-graded-exercise-effects-on-nk-cell-degranulation-markers-lamp-1-lamp-2-and-cd8-cd38-in-chronic-fatigue-syndrome-myalgic-encephalomyelitis
#10
Suzanne Broadbent, Rosanne Coutts
There is substantial evidence of immune system dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) but little is understood of exercise training effects on lymphocyte function in this illness. This study investigated whether graded and intermittent exercise improved CD8(+) lymphocyte activation and natural killer cell degranulation markers compared to no exercise. Twenty-four chronic fatigue syndrome (CFS) patients (50.2 ± 10 year) were randomized to graded exercise (GE), intermittent exercise (IE) or usual care (UC) groups; a control group (CTL) of 18 matched sedentary non-CFS/ME participants were included for immunological variable comparisons...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28270454/perforin-and-cd107a-testing-are-superior-to-nk-cell-function-testing-for-screening-patients-for-genetic-hlh
#11
Tamar S Rubin, Kejian Zhang, Carrie Gifford, Adam Lane, Jack J Bleesing, Rebecca A Marsh
Primary HLH (hemophagocytic lymphohistiocytosis) can be caused by bi-allelic mutations in PRF1, encoding perforin, or UNC13D, STXBP2, STX11, RAB27A, LYST and AP3B1, encoding proteins involved in cytotoxic lymphocyte degranulation. Natural killer (NK) cell cytotoxicity assays can quickly screen for all these genetic diseases, facilitating treatment, but combining NK cell perforin expression and CD107a upregulation tests can as well. To determine the relative diagnostic accuracies for each approach, we retrospectively reviewed screening test performance in 1614 patients referred for HLH evaluation...
March 7, 2017: Blood
https://www.readbyqxmd.com/read/28261217/expression-of-nkp46-splice-variants-in-nasal-lavage-following-respiratory-viral-infection-domain-1-negative-isoforms-predominate-and-manifest-higher-activity
#12
Yonat Shemer-Avni, Kiran Kundu, Avishai Shemesh, Michael Brusilovsky, Rami Yossef, Mesfin Meshesha, Semaria Solomon-Alemayehu, Shai Levin, Orly Gershoni-Yahalom, Kerry S Campbell, Angel Porgador
The natural killer (NK) cell activating receptor NKp46/NCR1 plays a critical role in elimination of virus-infected and tumor cells. The NCR1 gene can be transcribed into five different splice variants, but the functional importance and physiological distribution of NKp46 isoforms are not yet fully understood. Here, we shed light on differential expression of NKp46 splice variants in viral respiratory tract infections and their functional difference at the cellular level. NKp46 was the most predominantly expressed natural cytotoxicity receptor in the nasal lavage of patients infected with four respiratory viruses: respiratory syncytia virus, adenovirus, human metapneumovirus, or influenza A...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28239463/enhancing-adoptive-cancer-immunotherapy-with-v%C3%AE-2v%C3%AE-2-t-cells-through-pulse-zoledronate-stimulation
#13
Mohanad H Nada, Hong Wang, Grefachew Workalemahu, Yoshimasa Tanaka, Craig T Morita
BACKGROUND: Human γδ T cells expressing Vγ2Vδ2 T cell receptors monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Adoptive immunotherapy with Vγ2Vδ2 T cells has been used to treat cancer patients with partial and complete remissions. Most clinical trials and preclinical studies have used continuous zoledronate exposure to expand Vγ2Vδ2 cells where zoledronate is slowly diluted over the course of the culture...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28237837/a-novel-dna-vaccine-platform-enhances-neo-antigen-like-t-cell-responses-against-wt1-to-break-tolerance-and-induce-anti-tumor-immunity
#14
Jewell N Walters, Bernadette Ferraro, Elizabeth K Duperret, Kimberly A Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S Khan, Niranjan Y Sardesai, David B Weiner
Tumor-associated antigens have emerged as important immunotherapeutic targets in the fight against cancer. Germline tumor antigens, such as WT1, Wilms' tumor gene 1, are overexpressed in many human malignancies but have low expression in somatic tissues. Recent vaccination approaches to target WT1 have been hampered by poor in vivo immune potency, likely due to the conserved self-antigen nature of WT1. In this study, we use a novel synthetic micro-consensus SynCon DNA vaccine approach with the goal of breaking tolerance and increasing vaccine immune potency...
April 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28236454/il-15-super-agonist-alt-803-enhances-natural-killer-nk-cell-function-against-ovarian-cancer
#15
M Felices, S Chu, B Kodal, L Bendzick, C Ryan, A J Lenvik, K L M Boylan, H C Wong, A P N Skubitz, J S Miller, M A Geller
OBJECTIVE: Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. METHODS: NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation...
February 21, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28225449/ifn-%C3%AE-augments-natural-killer-mediated-antibody-dependent-cellular-cytotoxicity-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-major-histocompatibility-complex-class-1-downregulation
#16
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct natural killer (NK) cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon major histocompatibility complex class 1 (MHC-1) downregulation capacity. Here, we investigated if antibody-dependent cellular cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α prestimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1-infected patients (ART-suppressed or elite controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1-infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
March 13, 2017: AIDS
https://www.readbyqxmd.com/read/28171825/ex-vivo-expansion-of-cd3-depleted-cord-blood-mncs-in-the-presence-of-bone-marrow-stromal-cells-an-appropriate-strategy-to-provide-functional-nk-cells-applicable-for-cellular-therapy
#17
Ehteramolsadat Hosseini, Mehran Ghasemzadeh, Maedeh Kamalizad, Anthony P Schwarer
Considering umbilical cord blood (UCB) as a rich source of hematopoietic stem cells, we introduced a cost-effective approach to expand CD3(depleted) UCB-MNCs into functional NK cells. CD3(depleted) UCB-MNCs were expanded in the presence or absence of a feeder [bone marrow stem cells (BMSCs) or osteoblasts], with or without cytokines and their differentiation into NK cells was determined by flow cytometry. NK cell function was quantified by LAMP-1/CD107a expression, TNF-α/IFN-γ release, and LDH release/PI staining in targets...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28170096/circulating-nk-cells-and-their-subsets-in-beh%C3%A3-et-s-disease
#18
M S Hasan, P L Ryan, L A Bergmeier, F Fortune
Behçet's disease (BD) is an autoinflammatory, chronic relapsing/remitting disease of unknown aetiology with both innate and acquired immune cells implicated in disease pathogenesis. Peripheral blood natural killer (NK) cells and their CD56(Dim) /CD56(Bright) subsets were surface phenotyped using CD27 and CD16 surface markers in 60 BD patients compared to 60 healthy controls (HCs). Functional potential was assessed by production of interferon (IFN)-γ, granzyme B, perforin and the expression of degranulation marker CD107a...
May 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28154562/indian-long-term-non-progressors-show-broad-adcc-responses-with-preferential-recognition-of-v3-region-of-envelope-and-a-region-from-tat-protein
#19
Archana Kulkarni, Swarali Kurle, Ashwini Shete, Manisha Ghate, Sheela Godbole, Vijaya Madhavi, Stephen J Kent, Ramesh Paranjape, Madhuri Thakar
HIV-specific antibody-dependent cell cytotoxicity (ADCC) is likely to be important in governing protection from human immunodeficiency virus (HIV) and slowing disease progression. Little is known about the ADCC responses to HIV-1 subtype C. We characterized ADCC responses in HIV-1 subtype C-infected Indian subjects with slow disease progression and identified the dominant antigenic regions recognized by these antibodies. ADCC responses were measured in plasma from 34 long-term non-progressors (LTNPs), who were asymptomatic and maintained CD4 count above 500 cells/mm(3) for the last 7 years in the absence of antiretroviral therapy (ART), and 58 ART naïve progressors with CD4 count <500 cells/mm(3) against overlapping HIV-1 peptides using a flow cytometry-based antibody-dependent natural killer (NK) cell activation assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28139257/robust-8-color-flow-cytometry-panel-reveals-enhanced-effector-function-of-nkg2c-cd57-fc%C3%AE%C2%B5r%C3%AE-nk-cells-in-cmv-seropositive-human-blood-donors
#20
Thomas Nerreter, Stephan Zeiß, Thomas Herrmann, Hermann Einsele, Ruth Seggewiss-Bernhardt
Increasing evidence suggests that human NK cells may develop memory-like features. Here, we report the establishment of a robust 8-color flow cytometry panel that allows quantification and functional analysis of different memory-like NK cell subsets (NKG2C(+)/CD57(+), FcεRγ(-)) from relatively small blood samples. We could confirm previous publications reporting an enhanced prevalence of the mentioned memory-like NK cell subsets in CMV seropositive human donors and were able to show a clear congruence between enhanced expression of NKG2C and CD57, the absence of FcεRγ and CMV seropositivity supporting the hypothesis of memory-like NK cell development following viral infections...
January 25, 2017: Immunobiology
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