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https://www.readbyqxmd.com/read/28818566/a-synthetic-human-cytomegalovirus-pp65-ie1-fusion-antigen-efficiently-induces-and-expands-virus-specific-t-cells
#1
Ellen K Link, Christine Brandmüller, Yasemin Suezer, Stefanie Ameres, Asisa Volz, Andreas Moosmann, Gerd Sutter, Michael H Lehmann
Infection with human cytomegalovirus (HCMV) can cause severe complications in newborns and immunocompromised patients, and a prophylactic or therapeutic vaccine against HCMV is not available. Here, we generated a HCMV vaccine candidate fulfilling the regulatory requirements for GMP-compliant production and clinical testing. A novel synthetic fusion gene consisting of the coding sequences of HCMV pp65 and IE1 having a deleted nuclear localization sequence and STAT2 binding domain was introduced into the genome of the attenuated vaccinia virus strain MVA...
August 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#2
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28810601/comparative-study-of-dendritic-cells-matured-by-using-il-1%C3%AE-il-6-tnf-%C3%AE-and-prostaglandins-e2-for-different-time-span
#3
Xuejie Wu, Feng Xu, Jinliang Liu, Guiqiang Wang
Interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and prostaglandins E2 is considered as the standard cocktail for maturing dendritic cells (DCs). However, the appropriate time span for DC maturation with the standard cocktail remains unclear. The present study aimed to compare the differences between DCs matured with the standard cocktail for 24 and 48 h, respectively, and determine whether 24-h stimulation was sufficient for DC maturation. The findings demonstrated that, compared with DCs matured for 48 h, the levels of cluster of differentiation (CD)80, CD83, CD86 and programmed death-ligand 1 expression in DCs matured for 24 h were relatively lower...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28806760/endothelial-activation-and-dysfunction-in-severe-fever-with-thrombocytopenia-syndrome
#4
Xiao-Kun Li, Zhen-Dong Yang, Juan Du, Bo Xing, Ning Cui, Pan-He Zhang, Hao Li, Xiao-Ai Zhang, Qing-Bin Lu, Wei Liu
BACKGROUND: Pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) has not been well described yet. Recent studies indicate that SFTSV could replicate in endothelial cells. Here we performed a case-control study to determine whether endothelial activation/dysfunction occurred in SFTSV infection and to identify the biomarkers reflecting endothelial dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: In a case-control study of 134 SFTS patients and 68 healthy controls, serum levels of plasminogen activator inhibitor 1, tissue plasminogen activator, P-selectin, platelet endothelial cell adhesion molecular, CD40 ligand, E-selectin, vascular endothelial growth factor A, serum amyloid antigen 1 (SAA-1) and vascular cell adhesion molecular 1 were significantly enhanced in the patients than the controls (all P<0...
August 14, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28802400/mycobacterium-tuberculosis-myma-is-a-tlr2-agonist-that-activate-macrophages-and-a-th1-response
#5
Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma
Cell wall of Mycobacterium tuberculosis (M.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. MymA (Rv3083), a 55 kDa M.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following M.tb internalization in macrophage. In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engagement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28801616/circulating-cd40-and-scd40l-predict-changes-in-renal-function-in-subjects-with-chronic-kidney-disease
#6
Jeffrey X Xie, Helen Alderson, James Ritchie, Philip A Kalra, Yanmei Xie, Kaili Ren, Hanh Nguyen, Tian Chen, Pamela Brewster, Rajesh Gupta, Lance D Dworkin, Deepak Malhotra, Christopher J Cooper, Jiang Tian, Steven T Haller
Soluble CD40 ligand (sCD40L) has been implicated in the development of renal injury. The CD40 receptor exists in a soluble form, sCD40R, and has been shown to function as a competitive antagonist against CD40 activation. We analyzed whether plasma levels of sCD40L and sCD40R predict changes in renal function in an all-cause chronic kidney disease (CKD) cohort. Stratification of subjects based on sCD40L and sCD40R individually, as well as in combination, demonstrated that sCD40L was directly associated with declines in estimated glomerular filtration rate (eGFR)...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801357/the-autoimmune-risk-variant-ptpn22-c1858t-alters-b-cell-tolerance-at-discrete-checkpoints-and-differentially-shapes-the-naive-repertoire
#7
Genita Metzler, Xuezhi Dai, Christopher D Thouvenel, Socheath Khim, Tania Habib, Jane H Buckner, David J Rawlings
A common genetic variant in the gene encoding the protein tyrosine phosphatase nonreceptor type 22 (PTPN22 C1858T) has been linked to a wide range of autoimmune disorders. Although a B cell-intrinsic role in promoting disease has been reported, the mechanism(s) through which this variant functions to alter the preimmune B cell repertoire remains unknown. Using a series of polyclonal and transgenic self-reactive models harboring the analogous mutation in murine Ptpn22, we show evidence for enhanced BCR, B cell-activating factor receptor, and CD40 coreceptor programs, leading to broadly enhanced positive selection of B cells at two discrete checkpoints in the bone marrow and spleen...
August 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28801306/inducible-activation-of-myd88-and-cd40-in-car-t-cells-results-in-controllable-and-potent-antitumor-activity-in-preclinical-solid-tumor-models
#8
Melinda Mata, Claudia Gerken, Phuong Nguyen, Giedre Krenciute, David M Spencer, Stephen Gottschalk
Adoptive immunotherapy with T-cells expressing chimeric antigen receptors (CARs) has had limited success for solid tumors in early phase clinical studies. We reasoned that introducing into CAR T-cells an inducible co-stimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T-cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T-cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets in vitro relative to HER2ζ...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28796044/clinical-significance-of-costimulatory-molecules-cd40-cd40l-and-cd134-cd134l-in-coronary-heart-disease-a-case-control-study
#9
Jun Chen, Jian-Hao Li, Shan-Jun Zhao, Da-Yu Wang, Wen-Zhu Zhang, Wei-Jie Liang
The aim of the study was to evaluate the potential role of CD40/CD40 ligand (CD40L) and CD134/CD134 ligand (CD134L) in the development of coronary heart disease (CHD) via the performance of a case-control study.The research objects were 234 cases of CHD patients and 120 cases of well-matched normal controls. Following the separation of peripheral blood mononuclear cells (PBMCs), real-time quantitative PCR (qRT-PCR), Western blot, immunohistochemistry, and flow cytometry were applied for the detection of mRNA levels and expression levels of CD40/CD40L and CD134/CD134L; meanwhile, intercellular adhesion molecule-1 (ICAM-1) and Fas protein mRNA levels were detected using qRT-PCR...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28791011/leishmania-amazonensis-induced-camp-triggered-by-adenosine-a2b-receptor-is-important-to-inhibit-dendritic-cell-activation-and-evade-immune-response-in-infected-mice
#10
Amanda Braga Figueiredo, Míriam Conceição Souza-Testasicca, Tiago Wilson Patriarca Mineo, Luís Carlos Crocco Afonso
Differently from others Leishmania species, infection by the protozoan parasite L. amazonensis is associated with a lack of antigen-specific T-cell responses. Dendritic cells (DC) are essential for the innate immune response and for directing the differentiation of T-helper lymphocytes. Previously, we showed that L. amazonensis infection impairs DC activation through the activation of adenosine A2B receptor, and here, we evaluated the intracellular events triggered by this receptor in infected cells. To this aim, bone marrow-derived DC from C57BL/6J mice were infected with metacyclic promastigotes of L...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28780512/repeated-administration-of-dapirolizumab-pegol-in-a-randomised-phase-i-study-is-well-tolerated-and-accompanied-by-improvements-in-several-composite-measures-of-systemic-lupus-erythematosus-disease-activity-and-changes-in-whole-blood-transcriptomic-profiles
#11
Chris Chamberlain, Peter J Colman, Ann M Ranger, Linda C Burkly, Geoffrey I Johnston, Christian Otoul, Christian Stach, Miren Zamacona, Thomas Dörner, Murray Urowitz, Falk Hiepe
OBJECTIVES: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with diffuse immune cell dysfunction. CD40-CD40 ligand (CD40L) interaction activates B cells, antigen-presenting cells and platelets. CD40L blockade might provide an innovative treatment for systemic autoimmune disorders. We investigated the safety and clinical activity of dapirolizumab pegol, a polyethylene glycol conjugated anti-CD40L Fab' fragment, in patients with SLE. METHODS: This 32-week randomised, double-blind, multicentre study (NCT01764594) evaluated repeated intravenous administration of dapirolizumab pegol in patients with SLE who were positive for/had history of antidouble stranded DNA/antinuclear antibodies and were on stable doses of immunomodulatory therapies (if applicable)...
August 5, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28772243/daphnoretin-modulates-differentiation-and-maturation-of-human-dendritic-cells-through-down-regulation-of-c-jun-n-terminal-kinase
#12
Chien-An Chen, Chien-Kuo Liu, Ming-Ling Hsu, Chih-Wen Chi, Chun-Chuan Ko, Jian-Syun Chen, Cheng-Ta Lai, Hen-Hong Chang, Tzung-Yan Lee, Yuen-Liang Lai, Yu-Jen Chen
Daphnoretin, an active constituent of Wikstroemia indica C.A. Meys, has been shown possessing anti-cancer activity. In this study, we examined the effect of daphnoretin on differentiation and maturation of human myeloid dendritic cells (DCs). After treatment with daphnoretin (0, 1.1, 3.3, 10 and 30μM) to initiate monocytes, the recovery rate of DCs was reduced in a dose-dependent manner. The mature DCs differentiated in the presence of daphnoretin had fewer and shorter dendrites. Daphnoretin modulated DCs differentiation and maturation in terms of lower expression of CD1a, CD40, CD83, DC-SIGN, and HLA-DR...
July 31, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28769101/allostimulatory-capacity-of-conditionally-immortalized-proximal-tubule-cell-lines-for-bioartificial-kidney-application
#13
Milos Mihajlovic, Lambertus P van den Heuvel, Joost G Hoenderop, Jitske Jansen, Martijn J Wilmer, Annemarie J F Westheim, Wil A Allebes, Dimitrios Stamatialis, Luuk B Hilbrands, Rosalinde Masereeuw
Novel renal replacement therapies, such as a bioartificial kidney (BAK), are needed to improve current hemodialysis treatment of end-stage renal disease (ESRD) patients. As BAK applications may reveal safety concerns, we assessed the alloimmunization and related safety aspects of readily available conditionally immortalized human proximal tubule epithelial cell (ciPTEC) lines to be used in BAK. Two ciPTEC lines, originally derived from urine and kidney tissue, were characterized for the expression and secretion of relevant molecules involved in alloimmunization and inflammatory responses, such as HLA class-I, HLA-DR, CD40, CD80, CD86, as wells as soluble HLA class I and proinflammatory cytokines (IL-6, IL-8 and TNF-α)...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768709/co-stimulatory-function-in-primary-germinal-center-responses-cd40-and-b7-are-required-on-distinct-antigen-presenting-cells
#14
Masashi Watanabe, Chiharu Fujihara, Andrea J Radtke, Y Jeffrey Chiang, Sumeena Bhatia, Ronald N Germain, Richard J Hodes
T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production...
August 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28767735/engaging-the-cd40-cd40l-pathway-augments-t-helper-cell-responses-and-improves-control-of-mycobacterium-tuberculosis-infection
#15
Jonathan Kevin Sia, Erica Bizzell, Ranjna Madan-Lala, Jyothi Rengarajan
Mycobacterium tuberculosis (Mtb) impairs dendritic cell (DC) functions and induces suboptimal antigen-specific CD4 T cell immune responses that are poorly protective. Mucosal T-helper cells producing IFN-γ (Th1) and IL-17 (Th17) are important for protecting against tuberculosis (TB), but the mechanisms by which DCs generate antigen-specific T-helper responses during Mtb infection are not well defined. We previously reported that Mtb impairs CD40 expression on DCs and restricts Th1 and Th17 responses. We now demonstrate that CD40-dependent costimulation is required to generate IL-17 responses to Mtb...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28767693/dendritic-cells-that-phagocytose-apoptotic-macrophages-loaded-with-mycobacterial-antigens-activate-cd8-t-cells-via-cross-presentation
#16
Patricia Espinosa-Cueto, Alejandro Magallanes-Puebla, Carlos Castellanos, Raul Mancilla
While homeostatic apoptosis is immunologically silent, macrophage apoptosis during Mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. To examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nuclei of the dying cells...
2017: PloS One
https://www.readbyqxmd.com/read/28766890/inkt-cell-activation-plus-t-cell-transfer-establishes-complete-chimerism-in-a-murine-sublethal-bone-marrow-transplant-model
#17
Rumi Ishii, Toshihito Hirai, Satoshi Miyairi, Kazuya Omoto, Masayoshi Okumi, Yasuyuki Ishii, Kazunari Tanabe
Transplant tolerance induction makes it possible to preserve functional grafts for a lifetime without immunosuppressants. One powerful method is to generate mixed hematopoietic chimeras in recipients by adoptive transfer of donor-derived bone marrow cells (BMCs). In our murine transplantation model, we established a novel method for mixed chimera generation using sublethal irradiation, CD40-CD40L blockade, and invariant natural killer T-cell activation. However, numerous BMCs that are required to achieve stable chimerism makes it difficult to apply this model for human transplantation...
August 2, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28762863/dendritic-cells-maturated-by-co-culturing-with-hiv-1-latently-infected-jurkat-t-cells-or-stimulating-with-aids-associated-pathogens-secrete-tnf-alpha-to-reactivate-hiv-1-from-latency
#18
Xiao-Xin Ren, Li Ma, Wei-Wei Sun, Wen-Dong Kuang, Tai-Sheng Li, Xia Jin, Jian-Hua Wang
Elucidation of mechanisms underlying the establishment, maintenance of and reactivation from HIV-1 latency is essential for the development of therapeutic strategies aimed at eliminating HIV-1 reservoirs. Microbial translocation, as a consequence of HIV-1-induced deterioration of host immune system, is known to result in a systemic immune activation and transient outbursts of HIV-1 viremia in chronic HIV-1 infection. How these microbes cause the robust HIV-1 reactivation remains elusive. Dendritic cells (DCs) have previously been shown to reactivate HIV-1 from latency; however, the precise role of DCs in reactivating HIV-1 from latently infected T-cell remains obscure...
August 1, 2017: Virulence
https://www.readbyqxmd.com/read/28762633/platelet-activation-and-clotting-cascade-activation-by-dialyzers-designed-for-high-volume-online-hemodiafiltration
#19
Kamonwan Tangvoraphonkchai, Anne Riddell, Andrew Davenport
INTRODUCTION: Hemodialysis patients are pro-thrombotic. Higher volume online postdilutional hemodiafiltration (OL-HDF), with increasing hematocrit increases the risk of clotting in the extracorporeal circuit (ECC). We wished to determine whether OL-HDF increased platelet activation and ECC clotting. METHODS: Coagulation parameters, platelet, white cell, and endothelial activation markers were measured at the start and end of dialysis sessions in 10 patients and also pre- and post-dialyzer after 15 minutes using two different dialyzers designed for high volume OL-HDF; cellulose triacetate (TAGP) and polysulphone (PS), and polyvinylpyrrolidone (PVP)...
August 1, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28753651/schistosome-egg-antigens-including-the-glycoprotein-ipse-alpha-1-trigger-the-development-of-regulatory-b-cells
#20
Simone Haeberlein, Katja Obieglo, Arifa Ozir-Fazalalikhan, Mathilde A M Chayé, Henrike Veninga, Luciën E P M van der Vlugt, Astrid Voskamp, Louis Boon, Joke M M den Haan, Lotte B Westerhof, Ruud H P Wilbers, Arjen Schots, Gabriele Schramm, Cornelis H Hokke, Hermelijn H Smits
Infection with the helminth Schistosoma (S.) mansoni drives the development of interleukin (IL)-10-producing regulatory B (Breg) cells in mice and man, which have the capacity to reduce experimental allergic airway inflammation and are thus of high therapeutic interest. However, both the involved antigen and cellular mechanisms that drive Breg cell development remain to be elucidated. Therefore, we investigated whether S. mansoni soluble egg antigens (SEA) directly interact with B cells to enhance their regulatory potential, or act indirectly on B cells via SEA-modulated macrophage subsets...
July 2017: PLoS Pathogens
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