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https://www.readbyqxmd.com/read/28761354/pd-1-blockade-restores-impaired-function-of-ex-vivo-expanded-cd8-t-cells-and-enhances-apoptosis-in-mismatch-repair-deficient-epcam-pd-l1-cancer-cells
#1
Rajeev Kumar, Fang Yu, Yuan-Huan Zhen, Bo Li, Jun Wang, Yuan Yang, Hui-Xin Ge, Ping-Sheng Hu, Jin Xiu
BACKGROUND: Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy. METHODS: The cytotoxic function of expanded CD8(+) CTLs and interactions with tumor cells investigated after blocking of PD-1...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28737711/the-effects-of-artemisinin-on-the-cytolytic-activity-of-natural-killer-nk-cells
#2
Youn Kyung Houh, Kyung Eun Kim, Sunyoung Park, Dae Young Hur, Seonghan Kim, Daejin Kim, Sa Ik Bang, Yoolhee Yang, Hyun Jeong Park, Daeho Cho
Artemisinin, a chemical compound used for the treatment of malaria, has been known to show anti-cancer activity. However, the effect of this chemical on natural killer (NK) cells, which are involved in tumor killing, remains unknown. Here, we demonstrate that artemisinin exerts a potent anti-cancer effect by activating NK cells. NK-92MI cells pre-treated with artemisinin were subjected to a cytotoxicity assay using K562 cells. The results showed that artemisinin significantly enhances the cytolytic activity of NK cells in a dose-dependent manner...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28719652/long-term-follow-up-of-human-t-cell-responses-to-conserved-hiv-1-regions-elicited-by-dna-simian-adenovirus-mva-vaccine-regimens
#3
Nathifa Moyo, Nicola J Borthwick, Edmund G Wee, Silvia Capucci, Alison Crook, Lucy Dorrell, Tomáš Hanke
BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition...
2017: PloS One
https://www.readbyqxmd.com/read/28708886/kir3dl01-upregulation-on-gut-natural-killer-cells-in-response-to-siv-infection-of-kir-and-mhc-class-i-defined-rhesus-macaques
#4
Moritz Ries, Matthew R Reynolds, Ksenia Bashkueva, Kristin Crosno, Saverio Capuano, Trent M Prall, Roger Wiseman, David H O'Connor, Eva G Rakasz, Hajime Uno, Jeffrey D Lifson, David T Evans
Natural killer cells provide an important early defense against viral pathogens and are regulated in part by interactions between highly polymorphic killer-cell immunoglobulin-like receptors (KIRs) on NK cells and their MHC class I ligands on target cells. We previously identified MHC class I ligands for two rhesus macaque KIRs: KIR3DL01 recognizes Mamu-Bw4 molecules and KIR3DL05 recognizes Mamu-A1*002. To determine how these interactions influence NK cell responses, we infected KIR3DL01+ and KIR3DL05+ macaques with and without defined ligands for these receptors with SIVmac239, and monitored NK cell responses in peripheral blood and lymphoid tissues...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28678607/hiv-env-conserved-element-dna-vaccine-alters-immunodominance-in-macaques
#5
Xintao Hu, Antonio Valentin, Margherita Rosati, Siriphan Manocheewa, Candido Alicea, Bhabadeb Chowdhury, Jenifer Bear, Kate E Broderick, Niranjan Y Sardesai, Sylvie Le Gall, James I Mullins, George N Pavlakis, Barbara K Felber
Sequence diversity and immunodominance are major obstacles in the design of an effective vaccine against HIV. HIV Env is a highly-glycosylated protein composed of 'conserved' and 'variable' regions. The latter contains immunodominant epitopes that are frequently targeted by the immune system resulting in the generation of immune escape variants. This work describes 12 regions in HIV Env that are highly conserved throughout the known HIV M Group sequences (Env CE), and are poorly immunogenic in macaques vaccinated with full-length Env expressing DNA vaccines...
July 5, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28655861/in-silico-modeling-identifies-cd45-as-a-regulator-of-il-2-synergy-in-the-nkg2d-mediated-activation-of-immature-human-nk-cells
#6
Sayak Mukherjee, Helle Jensen, William Stewart, David Stewart, William C Ray, Shih-Yu Chen, Garry P Nolan, Lewis L Lanier, Jayajit Das
Natural killer (NK) cells perform immunosurveillance of virally infected and transformed cells, and their activation depends on the balance between signaling by inhibitory and activating receptors. Cytokine receptor signaling can synergize with activating receptor signaling to induce NK cell activation. We investigated the interplay between the signaling pathways stimulated by the cytokine interleukin-2 (IL-2) and the activating receptor NKG2D in immature (CD56(bright)) and mature (CD56(dim)) subsets of human primary NK cells using mass cytometry experiments and in silico modeling...
June 27, 2017: Science Signaling
https://www.readbyqxmd.com/read/28649252/sexual-dimorphic-responses-in-lymphocytes-of-healthy-individuals-after-carica-papaya-consumption
#7
Nur Ramziahrazanah Jumat, Mun Yee Chong, Zainina Seman, Rosita Jamaluddin, Nyet Kui Wong, Maha Abdullah
Sexual dimorphism in immune response is widely recognized, but few human studies have observed this distinction. Food with endo-immunomodulatory potential may reveal novel sex-biased in vivo interactions. Immunomodulatory effects of Carica papaya were compared between healthy male and female individuals. Volunteers were given fixed meals supplemented with papaya for 2 days. Changes in blood immune profiles and hormone levels were determined. In females, total natural killer (NK) cell percentages decreased (12...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28624584/antibody-dependent-nk-cell-degranulation-as-a-marker-for-assessing-antibody-dependent-cytotoxicity-against-pandemic-2009-influenza-a-h1n1-infection-in-human-plasma-and-influenza-vaccinated-transchromosomic-bovine-intravenous-immunoglobulin-therapy
#8
Brian J Morrison, Jessica A Roman, Thomas C Luke, Nishith Nagabhushana, Kanakatte Raviprakash, Maya Williams, Peifang Sun
This study describes an antibody-dependent NK cell degranulation assay, as a biomarker to assess antibody-dependent cellular cytotoxicity (ADCC) response in influenza plasma and for antibody therapies against influenza infection. The concentration of neutralizing antibodies (NAbs) against the hemagglutinin receptor of influenza viruses is a current determinant in protection against infection, particularly following receipt of the seasonal influenza vaccine. However, this is a limited assessment of protection, because: (i) NAb titers that incur full protection vary; and (ii) NAb titers do not account for the entire breadth of antibody responses against viral infection...
June 15, 2017: Journal of Virological Methods
https://www.readbyqxmd.com/read/28607115/surface-lamp-2-is-an-endocytic-receptor-that-diverts-antigen-internalized-by-human-dendritic-cells-into-highly-immunogenic-exosomes
#9
Dario Armando Leone, Andrea Peschel, Markus Brown, Helga Schachner, Miriam J Ball, Marianna Gyuraszova, Ulrike Salzer-Muhar, Minoru Fukuda, Caterina Vizzardelli, Barbara Bohle, Andrew J Rees, Renate Kain
The lysosome-associated membrane protein (LAMP) family includes the dendritic cell endocytic receptors DC-LAMP and CD68, as well as LAMP-1 and LAMP-2. In this study we identify LAMP-1 (CD107a) and LAMP-2 (CD107b) on the surface of human monocyte-derived dendritic cells (MoDC) and show only LAMP-2 is internalized after ligation by specific Abs, including H4B4, and traffics rapidly but transiently to the MHC class II loading compartment, as does Ag conjugated to H4B4. However, pulsing MoDC with conjugates of primary (keyhole limpet hemocyanin; KLH) and recall (Bet v 1) Ags (H4B4*KLH and H4B4*Bet v 1) induced significantly less CD4 cell proliferation than pulsing with native Ag or Ag conjugated to control mAb (ISO*KLH and ISO*Bet v 1)...
June 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28607114/varicella-zoster-virus-specific-cellular-immune-responses-to-the-live-attenuated-zoster-vaccine-in-young-and-older-adults
#10
Adriana Weinberg, Jennifer Canniff, Nadine Rouphael, Aneesh Mehta, Mark Mulligan, Jennifer A Whitaker, Myron J Levin
The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28595619/cytokine-treatment-optimises-the-immunotherapeutic-effects-of-umbilical-cord-derived-msc-for-treatment-of-inflammatory-liver-disease
#11
Samantha F H de Witte, Ana M Merino, Marcella Franquesa, Tanja Strini, Johanna A A van Zoggel, Sander S Korevaar, Franka Luk, Madhu Gargesha, Lisa O'Flynn, Debashish Roy, Steve J Elliman, Philip N Newsome, Carla C Baan, Martin J Hoogduijn
BACKGROUND: Mesenchymal stromal cells (MSC) possess immunomodulatory properties and low immunogenicity, both crucial properties for their development into an effective cellular immunotherapy. They have shown benefit in clinical trials targeting liver diseases; however the efficacy of MSC therapy will benefit from improvement of the immunomodulatory and immunogenic properties of MSC. METHODS: MSC derived from human umbilical cords (ucMSC) were treated for 3 days in vitro with various inflammatory factors, interleukins, vitamins and serum deprivation...
June 8, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28572174/go-with-the-flow-perforin-and-cd107a-in-hlh
#12
Melissa R Hines, Kim E Nichols
No abstract text is available yet for this article.
June 1, 2017: Blood
https://www.readbyqxmd.com/read/28559404/peripheral-t-cell-reactivity-to-heat-shock-protein-70-and-its-cofactor-grpe-from-tropheryma-whipplei-is-reduced-in-patients-with-classical-whipple-s-disease
#13
Lucia Trotta, Kathleen Weigt, Katina Schinnerling, Anika Geelhaar-Karsch, Gerrit Oelkers, Federico Biagi, Gino Roberto Corazza, Kristina Allers, Thomas Schneider, Ulrike Erben, Verena Moos
Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response toward Tropheryma whipplei in genetically predisposed individuals. The cofactor GrpE of heat shock protein 70 (Hsp70) from T. whipplei was previously identified as a B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific proinflammatory T-cell responses. Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before levels of CD40L, CD69, perforin, granzyme B, CD107a, and gamma interferon (IFN-γ) were determined in T cells by flow cytometry...
August 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28537894/intratumoral-depletion-of-regulatory-t-cells-using-cd25-targeted-photodynamic-therapy-in-a-mouse-melanoma-model-induces-antitumoral-immune-responses
#14
Dong Sun Oh, Heegon Kim, Ji Eun Oh, Hi Eun Jung, Yun Soo Lee, Ji-Ho Park, Heung Kyu Lee
Tumor immunotherapy aims to overcome the immunosuppressive microenvironment within tumors, and various approaches have been developed. Tumor-associated T regulatory cells (Tregs) suppress the activation and expansion of tumor antigen-specific effector T cells, thus, providing a permissive environment for tumor growth. Therefore, optimal strategies need to be established to deplete tumor-infiltrated Tregs because systemic depletion of Tregs can result in reduced anti-tumor effector cells and autoimmunity. Here, to selectively deplete Tregs in tumors, we intratumorally injected anti-CD25 antibodies conjugated to Chlorin e6 (Ce6), a photosensitizer that absorbs light to generate reactive oxygen species...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526557/the-frog-skin-host-defense-peptide-frenatin-2-1s-enhances-recruitment-activation-and-tumoricidal-capacity-of-nk-cells
#15
Jelena M Pantic, Ivan P Jovanovic, Gordana D Radosavljevic, Nevena M Gajovic, Nebojsa N Arsenijevic, J Michael Conlon, Miodrag L Lukic
Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity...
May 16, 2017: Peptides
https://www.readbyqxmd.com/read/28513532/natural-killer-cells-response-to-il-2-stimulation-is-distinct-between-ascites-with-the-presence-or-absence-of-malignant-cells-in-ovarian-cancer-patients
#16
Rodrigo Fernandes da Silva, Adriana Yoshida, Daniela Maira Cardozo, Rodrigo Menezes Jales, Silke Paust, Sophie Derchain, Fernando Guimarães
Peritoneal ascites are a distinguishable feature of patients with advanced epithelial ovarian cancer (EOC). The presence of different lymphocyte subsets has been reported in EOC-associated ascites, which also can or not contain malignant cells. The goal of this study was to analyze the functional characteristics of natural killer (NK) cells from EOC-associated ascites in terms of their expression of activating receptors and ascites' contents of lymphocyte subtypes, cytokine profile and presence of EOC cells...
May 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28501938/zoledronic-acid-renders-human-m1-and-m2-macrophages-susceptible-to-v%C3%AE-2-%C3%AE-%C3%AE-t-cell-cytotoxicity-in-a-perforin-dependent-manner
#17
Daniel W Fowler, John Copier, Angus G Dalgleish, Mark D Bodman-Smith
Vδ2(+) T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2(+) T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. In this study we focussed on macrophages (Mϕs), as these cells have been shown to take up ZA...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28499490/frequent-inoculations-with-radiation-attenuated-sporozoite-is-essential-for-inducing-sterile-protection-that-correlates-with-a-threshold-level-of-plasmodia-liver-stage-specific-cd8-t-cells
#18
Hardik Patel, Naveen Yadav, Rajesh Parmar, Satish Patel, Agam P Singh, Neeta Shrivastava, Sarat K Dalai
Whole sporozoite vaccine (WSV) is shown to induce sterile protection that targets Plasmodium liver-stage infection. There are many underlying issues associated with induction of effective sterile protracted protection. In this study, we have addressed how the alterations in successive vaccine regimen could possibly affect the induction of sterile protection. We have demonstrated that the pattern of vaccination with RAS (radiation attenuated sporozoites) induces varying degrees of protection among B6 mice. Animals receiving four successive doses generated 100% sterile protection...
July 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28498953/pathological-role-of-anti-cd4-antibodies-in-hiv-infected-immunologic-non-responders-under-viral-suppressive-antiretroviral-therapy
#19
Zhenwu Luo, Zhen Li, Lisa Martin, Zhuang Wan, Eric G Meissner, Enrique Espinosa, Hao Wu, Xiaocong Yu, Pingfu Fu, Maria Anna Julia Westerink, J Michael Kilby, Jennifer Wu, Lei Huang, Sonya L Heath, Zihai Li, Wei Jiang
Increased mortality and morbidity occurs in human immunodeficiency virus (HIV)-infected patients who fail to increase CD4+ T cell counts despite achieving viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 IgGs were found in HIV+ immunologic non-responders (CD4+ T cell counts ≤ 350 cells/μl) compared to HIV+ immunologic responders (CD4+ T cell counts ≥ 500 cells/μl) and healthy controls. Higher plasma level of anti-CD4 IgG correlated with blunted CD4+ T cell recovery...
May 11, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28495463/development-of-an-animal-model-of-progressive-vaccinia-in-nu-nu-mice-and-the-use-of-bioluminescence-imaging-for-assessment-of-the-efficacy-of-monoclonal-antibodies-against-vaccinial-b5-and-l1-proteins
#20
Marina Zaitseva, Antonia Thomas, Clement A Meseda, Charles Y K Cheung, Claudia G Diaz, Yan Xiang, Shane Crotty, Hana Golding
Bioluminescence imaging (BLI) was used to follow dissemination of recombinant vaccinia virus (VACV) expressing luciferase (IHD-J-Luc) in BALB/c nu/nu mice treated post-challenge with monoclonal antibodies (MAbs) against L1 and B5 VACV proteins in a model of Progressive Vaccinia (PV). Areas Under the flux Curve (AUC) were calculated for viral loads in multiple organs in individual mice. Following scarification with 10(5) pfu, IHD-J-Luc VACV undergoes fast replication at the injection site and disseminates rapidly to the inguinal lymph nodes followed by spleen, liver, and axillary lymph nodes within 2-3 days and before primary lesions are visible at the site of scarification...
May 8, 2017: Antiviral Research
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