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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
#1
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
#2
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...
February 1, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28170096/circulating-nk-cells-and-their-subsets-in-beh%C3%A3-et-s-disease
#3
Md Samiul Hasan, Paul L Ryan, Lesley A Bergmeier, Farida Fortune
Behçet's Disease (BD) is an auto-inflammatory, 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...
February 7, 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
#4
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
#5
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
https://www.readbyqxmd.com/read/28125549/o-001-a-diagnostic-approach-of-immune-dysregulation-on-very-early-onset-ibd
#6
Judith Kelsen, Noor Dawany, Maire Conrad, Kathleen Sullivan, Edward Behrens, Marcella Devoto
BACKGROUND: Immune deficiencies have been associated with inflammatory bowel disease (IBD), and are reported to be particularly enriched in patients with very early-onset IBD (VEO-IBD). However, the actual frequency of primary immune deficiencies in an unselected cohort of patients with VEO-IBD is not known, nor is the optimal screening approach for this population. This study was undertaken to identify a diagnostic approach that will enhance identification of children with primary immune deficiencies who present with VEO-IBD...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28076903/slamf7-engagement-restores-defective-effector-cd8-t-cells-activity-in-response-to-foreign-antigens-in-systemic-lupus-erythematosus
#7
Denis Comte, Maria P Karampetsou, Nobuya Yoshida, Katalin Kis-Toth, Vasileios C Kyttaris, George C Tsokos
OBJECTIVE: Effector CD8+ T cell function is impaired in SLE and associated with compromised ability to fight infections. SLAMF7 engagement has been shown to enhance NK cell degranulation. Thus, we characterized the expression and function of SLAMF7 on CD8+ T cells subsets isolated from peripheral blood of SLE patients and healthy subjects. METHODS: CD8+ T cell subset distribution, SLAMF7 expression and cytolytic enzyme expression (perforin, GzmA, GzmB) were monitored on cells isolated from SLE patients and healthy controls by flow cytometry...
January 11, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28076376/increased-natural-killer-cell-activation-in-hiv-infected-immunologic-non-responders-correlates-with-cd4-t-cell-recovery-after-antiretroviral-therapy-and-viral-suppression
#8
Zhenwu Luo, Zhen Li, Lisa Martin, Zhiliang Hu, Hao Wu, Zhuang Wan, Michael Kilby, Sonya L Heath, Lei Huang, Wei Jiang
The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as "immunologic responders" and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as "immunologic non-responders"...
2017: PloS One
https://www.readbyqxmd.com/read/28060015/ifn-%C3%AE-augments-nk-mediated-antibody-dependent-cellular-cytotoxicity-adcc-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-mhc-i-downregulation
#9
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct NK cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon MHC-I 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 pre-stimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1 infected subjects (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...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28056887/therapeutic-vaccine-targeting-epstein-barr-virus-latent-protein-lmp1-suppresses-lmp1-expressing-tumor-growth-and-metastasis-in-vivo
#10
Mei-Chun Lin, Yong-Chong Lin, Syue-Ting Chen, Tai-Horng Young, Pei-Jen Lou
BACKGROUND: In endemic area, nasopharyngeal carcinoma (NPC) tumor cells harbor EBV latent infection and expresses viral antigens such as EBNA1, LMP1 and LMP2. In this study, we established a NPC-mimicry animal model and assessed the therapeutic potential of LMP1 vaccine. METHODS: Animal models were established by injection of LMP1-expressing TC-1 cells in C57BL6/J mice subcutaneously or through tail veins. pcDNA3.1 empty vector or LMP1/pcDNA3.1 vaccine was delivered by a helium-driven gene gun...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28053099/hcmv-specific-cd4-t-cells-are-poly-functional-and-can-respond-to-hcmv-infected-dendritic-cells-in-vitro
#11
Sarah E Jackson, George X Sedikides, Gavin M Mason, Georgina Okecha, Mark R Wills
: Human cytomegalovirus (HCMV) infection and periodic re-activation is generally well controlled by the HCMV-specific T cell response in healthy people. While the CD8+ T cell response to HCMV has been extensively studied, the HCMV-specific CD4+ T cell effector response is not as well understood, especially in the context of direct interactions with HCMV infected cells. We screened the IFNγ and IL-10 response to 6 HCMV peptide pools (selected as the most frequently responded to in our previous studies: pp65, pp71, IE1, IE2, gB and US3) in 84 donors, aged 23 - 74 years...
January 4, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28018364/nkg2a-expressing-natural-killer-cells-dominate-the-response-to-autologous-lymphoblastoid-cells-infected-with-epstein-barr-virus
#12
Olivia Hatton, Dara Marie Strauss-Albee, Nancy Q Zhao, Mikel D Haggadone, Judith Shanika Pelpola, Sheri M Krams, Olivia M Martinez, Catherine A Blish
Epstein-Barr virus (EBV) is a human γ-herpesvirus that establishes latency and lifelong infection in host B cells while achieving a balance with the host immune response. When the immune system is perturbed through immunosuppression or immunodeficiency, however, these latently infected B cells can give rise to aggressive B cell lymphomas. Natural killer (NK) cells are regarded as critical in the early immune response to viral infection, but their role in controlling expansion of infected B cells is not understood...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28004787/cross-protective-efficacy-of-dendritic-cells-targeting-conserved-influenza-virus-antigen-expressed-by-lactobacillus-plantarum
#13
Wen-Tao Yang, Shao-Hua Shi, Gui-Lian Yang, Yan-Long Jiang, Liang Zhao, Yu Li, Chun-Feng Wang
Avian influenza virus (AIV) can infect birds and mammals, including humans, and are thus a serious threat to public health. Vaccination is vital for controlling AIV circulation. In this study, we generated a recombinant lactobacillus expressing the NP-M1-DCpep of H9N2 avian influenza virus and evaluated the activation effect of NC8-pSIP409-NP-M1-DCpep on dendritic cells (DCs) in a mouse model. The specific mucosal antibody responses and B and T cell responses in lymphoid tissues were also characterized. Importantly, we confirmed that specific CD8 T cells presented in vitro and antigen-specific cytotoxicity (activated the expression of CD107a) and in vivo antigen-specific cytotoxicity after vaccination...
December 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28003815/degranulation-response-in-cytotoxic-rat-lymphocytes-measured-with-a-novel-cd107a-antibody
#14
Amanda Sudworth, Ke-Zheng Dai, John T Vaage, Lise Kveberg
Measuring degranulation through CD107a expression has become an advantageous tool for testing the functional capacity of cytotoxic cells. Such functional studies have been hampered in the rat by the lack of a suitable anti-rat CD107a antibody. In this study, we report a novel hybridoma generated by immunizing Armenian inbred hamsters with transfected Chinese hamster ovary cells expressing CD107a. The SIM1 clone exhibited specific reactivity with CD107a and measured degranulation from natural killer (NK) cells stimulated with target cells or mAb crosslinking of their activating receptors...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27979840/early-effector-t-lymphocytes-coexpress-multiple-inhibitory-receptors-in-primary-non-small-cell-lung-cancer
#15
Elena Tassi, Giulia Grazia, Claudia Vegetti, Ilaria Bersani, Giulia Bertolini, Alessandra Molla, Paola Baldassari, Francesca Andriani, Luca Roz, Gabriella Sozzi, Ugo Pastorino, Roberta Mortarini, Andrea Anichini
Clinical efficacy of PD-1/PD-L1 targeting relies upon the reactivation of tumor-specific but functionally impaired PD-1(+) T cells present before therapy. Thus, analyzing early-stage primary tumors may reveal the presence of T cells that are not yet functionally impaired. In this study, we report that activated (HLA-DR(+)) T cells with an effector memory (TEM) profile are enriched in such lesions. Tumor-infiltrating lymphocytes coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3, and TIGIT, but also displayed a recently activated, nonexhausted phenotype...
December 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27941937/nkp30-nk-cells-are-associated-with-hbv-control-during-pegylated-interferon-alpha-2b-therapy-of-chronic-hepatitis-b
#16
Xiaokun Shen, Binqing Fu, Yanyan Liu, Chuang Guo, Ying Ye, Rui Sun, Jiabin Li, Zhigang Tian, Haiming Wei
A pressing need exists for improved therapeutic options for chronic hepatitis B (CHB). Pegylated-interferon-alpha (Peg-IFN-α) achieves sustained off-treatment responses in many cases because of its direct anti-viral effects and regulation of the immune response. However, non-responsiveness to Peg-IFN-α is frequent, and the mechanism is poorly understood. In this study, we found that the frequency and absolute number of NKp30(+) natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders...
December 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27907031/in-vitro-pre-clinical-validation-of-suicide-gene-modified-anti-cd33-redirected-chimeric-antigen-receptor-t-cells-for-acute-myeloid-leukemia
#17
Kentaro Minagawa, Muhammad O Jamil, Mustafa Al-Obaidi, Larisa Pereboeva, Donna Salzman, Harry P Erba, Lawrence S Lamb, Ravi Bhatia, Shin Mineishi, Antonio Di Stasi
BACKGROUND: Approximately fifty percent of patients with acute myeloid leukemia can be cured with current therapeutic strategies which include, standard dose chemotherapy for patients at standard risk of relapse as assessed by cytogenetic and molecular analysis, or high-dose chemotherapy with allogeneic hematopoietic stem cell transplant for high-risk patients. Despite allogeneic hematopoietic stem cell transplant about 25% of patients still succumb to disease relapse, therefore, novel strategies are needed to improve the outcome of patients with acute myeloid leukemia...
2016: PloS One
https://www.readbyqxmd.com/read/27885748/protective-efficacy-and-hepatitis-b-virus-clearance-in-mice-enhanced-by-cell-mediated-immunity-with-novel-prime-boost-regimens
#18
X Chuai, P Chen, H Chen, W Wang, Y Deng, L Ruan, W Li, W Tan
In this study, anti-hepatitis B virus (HBV) immunity was evaluated in mice using several regimens of the HBV recombinant protein vaccine HBSS1 that expressed in CHO cells containing S (1-223 aa) and preS1 (21-47 aa) and recombinant adenovirus rAdSS1 vaccine. Further, the protective efficacy of these vaccine regimens was studied in a mouse model. High titres of antigen-specific antibodies and neutralizing activity were elicited in mice after vaccination. However, robust multi-antigen (preS1 and S)-specific cell-mediated immunity (CMI) was only detected in mice primed with HBSS1 and boosted with rAdSS1...
November 25, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27862177/decreased-percentage-of-nkg2d-nk-cells-in-patients-with-incident-onset-of-type-1-diabetes
#19
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
#20
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
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