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https://www.readbyqxmd.com/read/28551462/rationalization-of-a-nanoparticle-based-nicotine-nanovaccine-as-an-effective-next-generation-nicotine-vaccine-a-focus-on-hapten-localization
#1
Zongmin Zhao, Yun Hu, Theresa Harmon, Paul Pentel, Marion Ehrich, Chenming Zhang
A lipid-polymeric hybrid nanoparticle-based next-generation nicotine nanovaccine was rationalized in this study to combat nicotine addiction. A series of nanovaccines, which had nicotine-haptens localized on carrier protein (LPKN), nanoparticle surface (LPNK), or both (LPNKN), were designed to study the impact of hapten localization on their immunological efficacy. All three nanovaccines were efficiently taken up and processed by dendritic cells. LPNKN induced a significantly higher immunogenicity against nicotine and a significantly lower anti-carrier protein antibody level compared to LPKN and LPNK...
May 19, 2017: Biomaterials
https://www.readbyqxmd.com/read/28551327/t-cell-transcription-factor-gata-3-is-an-immunophenotypic-marker-of-acute-leukemias-with-t-cell-differentiation
#2
David M Dorfman, Elizabeth A Morgan, Ashley Pelton, Christine Unitt
T cell transcription factor GATA-3, known to play a role in early T cell development and in the development of T cell neoplasms, is expressed at high levels in fetal and adult thymus, as well as in acute leukemias with T-cell differentiation, including T lymphoblastic leukemia/lymphoma (22/22 cases), early T cell precursor (ETP) lymphoblastic leukemia (11/11 cases), and mixed phenotype acute leukemia, T/myeloid (4/5 cases), but only rarely in acute myeloid leukemia/myeloid sarcoma (1/36 cases), and not in B lymphoblastic leukemia (0/16 cases)...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#3
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550203/socs1-is-a-key-molecule-that-prevents-regulatory-t-cell-plasticity-under-inflammatory-conditions
#4
Reiko Takahashi, Hiroko Nakatsukasa, Shunichi Shiozawa, Akihiko Yoshimura
We previously showed that regulatory T cells (Tregs) from T cell-specific Socs1-deficient mice (Socs1(fl/fl)Lck-Cre(+) mice) easily convert into Th1- or Th17-like cells (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs in Socs1(fl/fl)Lck-Cre(+) mice are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs in vivo, in this study we analyzed Treg-specific Socs1-deficient mice (Socs1(fl/fl)Foxp3(YFP-Cre) mice). These mice developed dermatitis, splenomegaly, and lymphadenopathy that were much milder than those in Socs1(fl/fl)Lck-Cre(+) mice...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28549432/dendritic-cells-combined-with-tumor-cells-and-%C3%AE-galactosylceramide-induce-a-potent-therapeutic-and-nk-cell-dependent-antitumor-immunity-in-b-cell-lymphoma
#5
Laura Escribà-Garcia, Carmen Alvarez-Fernández, Marta Tellez-Gabriel, Jorge Sierra, Javier Briones
BACKGROUND: Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells play a central role in tumor immunology since they are implicated in the coordination of innate and adaptive immune responses. These cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating interferon gamma (IFN-γ) production and cytokine secretion, which contribute to the enhancement of T cell activation...
May 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28549299/the-effect-of-feed-supplementation-with-effective-microorganisms-em-on-pro-and-anti-inflammatory-cytokine-concentrations-in-pigs
#6
Ewa Laskowska, Łukasz Jarosz, Zbigniew Grądzki
Effective microorganisms (EM) are used in numerous fields associated with agriculture. The beneficial effects of EM on the general health of pigs and on production parameters are also determined by the influence of these microbes on immunity. The aim of the study was to assess the effect of feed supplementation with EM on the concentration of pro- and anti-inflammatory cytokines in the serum and in a culture of PBMCs with and without ConA stimulation in pigs. ELISA kits were used to determine the cytokine levels in the porcine serum and the PBMC culture supernatants...
April 14, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28548891/immunological-characteristics-of-colitis-associated-with-anti-ctla-4-antibody-therapy
#7
Giorgos Bamias, Ioanna Delladetsima, Marina Perdiki, Spyros I Siakavellas, Dimitrios Goukos, George V Papatheodoridis, George L Daikos, Helen Gogas
Anti-CTL4-A therapy is associated with development of colitis. We characterized ipilimumab-associated colitis in nine melanoma patients (6 male, mean age: 55.3-yrs). Median value for diarrhea grade was 2, number of ipilimumab doses 2, and interval since last administration 3-wks. Endoscopic characteristics resembled inflammatory bowel disease and histology revealed predominance of plasmacytes or CD4+ T-cells. We observed significant upregulation of Th1 and Th17 effector pathways (>10-fold increase for IFN-γmRNA, >5-fold for IL-17A, p < 0...
May 26, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28546563/microbiota-in-t-cell-homeostasis-and-inflammatory-diseases
#8
REVIEW
Naeun Lee, Wan-Uk Kim
The etiology of disease pathogenesis can be largely explained by genetic variations and several types of environmental factors. In genetically disease-susceptible individuals, subsequent environmental triggers may induce disease development. The human body is colonized by complex commensal microbes that have co-evolved with the host immune system. With the adaptation to modern lifestyles, its composition has changed depending on host genetics, changes in diet, overuse of antibiotics against infection and elimination of natural enemies through the strengthening of sanitation...
May 26, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28546549/restimulation-induced-t-cell-death-through-ntb-a-sap-signaling-pathway-is-impaired-in-tuberculosis-patients-with-depressed-immune-responses
#9
Rodrigo E Hernández Del Pino, Joaquín M Pellegrini, Ana I Rovetta, Delfina Peña, Guadalupe I Álvarez, Agustín Rolandelli, Rosa M Musella, Domingo J Palmero, Alejandro Malbran, Virginia Pasquinelli, Verónica E García
Production of IFN-γ contributes to host defense against Mycobacterium tuberculosis (Mtb) infection. We previously demonstrated that Signaling lymphocytic activation molecule-associated protein (SAP) expression on cells from tuberculosis (TB) patients was inversely correlated with IFN-γ production. Here we first investigated the role of NK, T and B cell antigen (NTB-A)/SAP pathway in the regulation of Th1 response against Mtb. Upon antigen stimulation, NTB-A phosphorylation rapidly increases and afterwards modulates IFN-γ and IL-17 secretion...
May 26, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28546518/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#10
Nyamongo Onkoba, Ruth M Mumo, Horace Ochanda, Charles Omwandho, Hastings S Ozwara, Thomas G Egwang
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28546254/response-to-ustekinumab-inhibits-th1-and-th17-polarisation-in-a-giant-cell-arteritis-patient-by-samson-et-al
#11
Richard Conway, Ursula Fearon, Eamonn S Molloy
No abstract text is available yet for this article.
May 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28544850/pcpp-adjuvanted-respiratory-syncytial-virus-rsv-sf-subunit-vaccine-self-assembled-supramolecular-complexes-enable-enhanced-immunogenicity-and-protection
#12
Corinne Cayatte, Alexander Marin, Gaurav Manohar Rajani, Kirsten Schneider-Ohrum, Angie Snell Bennett, Jason D Marshall, Alexander K Andrianov
PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the post-fusion glycoprotein (RSV sF) of RSV, which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to Alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF-Alum formulations, suggesting an inherent immunostimulating activity of the polyphosphazene adjuvant...
May 25, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28544232/peripartum-cytokine-flares-in-a-multiethnic-cohort-of-chronic-hepatitis-b-carriers-does-not-correlate-with-hepatitis-b-virus-suppression-or-increased-risk-of-liver-disease
#13
Shivali S Joshi, Daniel Wong, Eliana Castillo, Mark G Swain, Carla S Coffin
PROBLEM: In chronic hepatitis B (CHB) carriers, alanine transaminase (ALT) flares are common in the peripartum period. There are limited data on immunological changes of pregnancy in CHB. We hypothesize that in pregnant CHB carriers, the Th1/Th2 cytokine ratio is altered resulting in changes in biochemical/virological and liver fibrosis markers. STUDY METHODS: Serum from 38 pregnant/post-partum CHB carriers (median age 32 years, 53% Asian, 8 HBeAg(+) ) was tested for HBV DNA, quantitative HBV surface antigen, ALT and liver fibrosis by transient elastography (TE)...
May 19, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28542921/cd40-mediated-signaling-influences-trafficking-tcr-expression-and-t-cell-pathogenesis-in-the-nod-model-of-type-1-diabetes
#14
Gisela M Vaitaitis, Dan M Waid, Martin G Yussman, David H Wagner
CD40 plays a critical role in the pathogenesis of type 1 diabetes (T1D). The mechanism of action however is undetermined, likely because CD40 expression has been grossly underestimated. CD40 is expressed on numerous cell types that now include T cells and pancreatic β cells. CD40(+) CD4(+) cells (TH40) prove highly pathogenic in NOD mice and in translational human T1D studies. We generated BDC2.5.CD40(-/-) and re-derived NOD.CD154(-/-) mice to better understand CD40 mechanism of action. Fully functional CD40 expression is required not only for T1D development but for insulitis...
May 19, 2017: Immunology
https://www.readbyqxmd.com/read/28542613/suppression-of-il-12p70-formation-by-il-2-or-following-macrophage-depletion-causes-t-cell-autoreactivity-leading-to-cns-demyelination-in-hsv-1-infected-mice
#15
Dhong Hyun Lee, Mandana Zandian, Jane Kuo, Kevin R Mott, Shuang Chen, Moshe Arditi, Homayon Ghiasi
We have established two mouse models of central nervous system (CNS) demyelination that differ from most other available models of multiple sclerosis (MS) in that they represent a mixture of viral and immune triggers. In the first model, ocular infection of different strains of mice with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination. In the second model, depletion of macrophages causes CNS demyelination in mice that are ocularly infected with wild-type (WT) HSV-1...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542586/antigen-delivery-to-dendritic-cells-shapes-human-cd4-and-cd8-t-cell-memory-responses-to-staphylococcus-aureus
#16
Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4+ and CD8+ T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4+ and CD8+ T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542438/chemically-induced-disseminated-pythiosis-in-balb-c-mice-a-new-experimental-model-for-pythium-insidiosum-infection
#17
Juliana S M Tondolo, Érico S Loreto, Pauline C Ledur, Francielli P K Jesus, Taiara M Silva, Glaucia D Kommers, Sydney H Alves, Janio M Santurio
Pythiosis is a severe and life-threatening disease that affects humans and various animal species. We report a model of vascular/disseminated pythiosis occurring after subcutaneous inoculation of 2 x 104 Pythium insidiosum zoospores/mL in immunocompromised BALB/c mice. For this model, we carried out two rounds of experiments. First, we evaluated two protocols of immunosuppression before inoculation: cyclophosphamide at 150 mg/kg (CYP group) and cyclophosphamide 200 mg/kg plus hydrocortisone acetate at 250 mg/kg (CYP+HCA group)...
2017: PloS One
https://www.readbyqxmd.com/read/28542175/single-sex-infection-with-female-schistosoma-mansoni-cercariae-mitigates-hepatic-fibrosis-after-secondary-infection
#18
Nicole Koslowski, Martina Sombetzki, Micha Loebermann, Robby Engelmann, Niels Grabow, Christoph H Österreicher, Michael Trauner, Brigitte Mueller-Hilke, Emil C Reisinger
BACKGROUND: Infection with Schistosoma spp. affects more than 258 million people worldwide. Current treatment strategies are mainly based on the anthelmintic Praziquantel, which is effective against adult worms but neither prevents re-infection nor cures severe liver damage. The best long-term strategy to control schistosomiasis may be to develop an immunization. Therefore, we designed a two-step Schistosoma mansoni infection model to study the immune-stimulating effect of a primary infection with either male or female cercariae, measured on the basis of TH1/TH2-response, granuloma size and hepatic fibrosis after a secondary bisexual S...
May 19, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28539888/safety-and-immunogenicity-of-a-human-epidermal-growth-factor-receptor-1-her1-based-vaccine-in-prostate-castration-resistant-carcinoma-patients-a-dose-escalation-phase-i-study-trial
#19
Iraida Caballero, Lazaro E Aira, Anabel Lavastida, Xitlally Popa, Javier Rivero, Joaquín González, Mónica Mesa, Narjara González, Kelly Coba, Patricia Lorenzo-Luaces, Barbara Wilkinson, Yuliannis Santiesteban, Yanela Santiesteban, Mayelin Troche, Eduardo Suarez, Tania Crombet, Belinda Sánchez, Angel Casacó, Amparo Macías, Zaima Mazorra
Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Activation of the human epidermal growth factor receptor 1 (HER1) in prostate cancer contributes to metastatic progression as well as to disease relapse. Here, we determined the toxicity and immunogenicity of a HER1-based cancer vaccine in CRPC patients included in a phase I clinical trial. CRPC patients (n = 24) were intramuscularly vaccinated with HER1 vaccine consisting of the extracellular domain of HER1 molecule (ECD) and very small size proteoliposome from Neisseria meningitidis (VSSP) and Montanide ISA-51 VG as adjuvants...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28539628/low-level-of-lck-kinase-in-th2-cells-limits-expression-of-cd4-co-receptor-and-s73-phosphorylation-of-transcription-factor-c-jun
#20
Yury V Shebzukhov, Silke Stanislawiak, Taisiya R Bezhaeva, Sergei A Nedospasov, Dmitry V Kuprash
The Src-family tyrosine kinase Lck is an enzyme associated with the CD4 and CD8 co-receptors and promoting signaling through the T cell receptor (TCR) complex. The levels of Lck expression and activity change during the development and differentiation of T cells. Here we show that Lck expression is higher in Th1 cells as compared to Th2 cells. Ectopic overexpression of Lck in Th2 cells results in increased expression of CD4 co-receptor and enhanced S73 phosphorylation of transcription factor c-Jun. Our findings indicate that TCR-mediated signaling in Th2 cells may be directly attenuated by Lck protein expression level...
May 24, 2017: Scientific Reports
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