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https://www.readbyqxmd.com/read/28076903/slamf7-engagement-restores-defective-effector-cd8-t-cells-activity-in-response-to-foreign-antigens-in-systemic-lupus-erythematosus
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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 (TIL) coexpressed PD-1 with the inhibitory receptors TIM-3, CTLA-4, LAG-3 and TIGIT, but also displayed a recently activated, non-exhausted 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
#10
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
#11
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
#12
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
#13
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
#14
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/27834032/identification-and-characterization-of-cd107a-as-a-marker-of-low-reactive-oxygen-species-in-chemoresistant-cells-in-colorectal-cancer
#15
Tomohiro Kitahara, Naotsugu Haraguchi, Hidekazu Takahashi, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Tsunekazu Mizushima, Hirofumi Yamamoto, Yuichiro Doki, Masaki Mori
BACKGROUND: Reactive oxygen species (ROS) generated by chemoradiotherapy lead to cancer cell death. Although ROS regulation mechanisms play important roles in chemoradioresistance, few markers exist that indicated intracellular ROS status. This study aimed to identify novel cell surface markers that represented intracellular ROS status to characterize cells with low ROS (ROS(low)) in colorectal cancer (CRC). METHODS: We used ROS indicators and an antibody array with 242 cell surface antibodies to identify markers of ROS(low) cells...
November 10, 2016: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/27830183/human-cytomegalovirus-infection-enhances-nk-cell-activity-in-vitro
#16
Astrid Tschan-Plessl, Martin Stern, Laurent Schmied, Christelle Retière, Hans H Hirsch, Christian Garzoni, Christian van Delden, Katia Boggian, Nicolas J Mueller, Christoph Berger, Jean Villard, Oriol Manuel, Pascal Meylan, Grzegorz Terszowski
BACKGROUND: Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive. METHODS: We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant...
July 2016: Transplantation Direct
https://www.readbyqxmd.com/read/27809856/t-cells-in-multiple-myeloma-display-features-of-exhaustion-and-senescence-at-the-tumor-site
#17
Claudia Zelle-Rieser, Shanmugapriya Thangavadivel, Rainer Biedermann, Andrea Brunner, Patrizia Stoitzner, Ella Willenbacher, Richard Greil, Karin Jöhrer
BACKGROUND: Multiple myeloma is an incurable plasma cell malignancy that is mostly restricted to the bone marrow. Cancer-induced dysfunction of cytotoxic T cells at the tumor site may be responsible for immune evasion and therapeutical failure of immunotherapies. Therefore, enhanced knowledge about the actual status of T cells in myeloma bone marrow is urgently needed. Here, we assessed the expression of inhibitory molecules PD-1, CTLA-4, 2B4, CD160, senescence marker CD57, and CD28 on T cells of naive and treated myeloma patients in the bone marrow and peripheral blood and collected data on T cell subset distribution in both compartments...
November 3, 2016: Journal of Hematology & Oncology
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
#18
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]
https://www.readbyqxmd.com/read/27733554/dna-prime-boost-vaccine-regimen-to-increase-breadth-magnitude-and-cytotoxicity-of-the-cellular-immune-responses-to-subdominant-gag-epitopes-of-simian-immunodeficiency-virus-and-hiv
#19
Xintao Hu, Antonio Valentin, Frances Dayton, Viraj Kulkarni, Candido Alicea, Margherita Rosati, Bhabadeb Chowdhury, Rajeev Gautam, Kate E Broderick, Niranjan Y Sardesai, Malcolm A Martin, James I Mullins, George N Pavlakis, Barbara K Felber
HIV sequence diversity and the propensity of eliciting immunodominant responses targeting variable regions of the HIV proteome are hurdles in the development of an effective AIDS vaccine. An HIV-derived conserved element (CE) p24(gag) plasmid DNA (pDNA) vaccine is able to redirect immunodominant responses to otherwise subdominant and often more vulnerable viral targets. By homology to the HIV immunogen, seven CE were identified in SIV p27(Gag) Analysis of 31 rhesus macaques vaccinated with full-length SIV gag pDNA showed inefficient induction (58% response rate) of cellular responses targeting these CE...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27727448/impaired-calcium-mobilization-in-natural-killer-cells-from-chronic-fatigue-syndrome-myalgic-encephalomyelitis-patients-is-associated-with-transient-receptor-potential-melastatin-3-ion-channels
#20
T Nguyen, S Johnston, L Clarke, P Smith, D Staines, S Marshall-Gradisnik
Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca(2+) ) cell signalling. Reduced TRPM3 protein expression has been identified in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca(2+) mobilization has yet to be determined. Fifteen CFS/ME patients (mean age 48·82 ± 9·83 years) and 25 healthy controls (mean age 39·2 ± 12·12 years) were examined. Isolated natural killer (NK) cells were labelled with fluorescent antibodies to determine TRPM3, CD107a and CD69 receptors on CD56(dim) CD16(+) NK cells and CD56(bright) CD16(dim/-) NK cells...
February 2017: Clinical and Experimental Immunology
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