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Yoko Motokawa, Michifumi Kokubo, Nobuo Kuwabara, Ken-Ichiro Tatematsu, Hideki Sezutsu, Hideyuki Takahashi, Koichi Sakakura, Kazuaki Chikamatsu, Shigeki Takeda
Recent clinical trials with the aim of developing tumor antigen (TA)-specific cancer vaccines against a number of malignancies have focused on the identification of TAs presented by tumor cells and recognized by T cells. In the present study, the TA melanoma antigen family A4 (MAGE-A4) protein was produced using a transgenic (TG) silkworm system. Using in vitro stimulation, it was subsequently determined whether MAGE-A4 protein induced MAGE-A4-specific T cells from peripheral blood mononuclear cells of healthy donors...
March 2018: Experimental and Therapeutic Medicine
Blaise Corthésy, Gilles Bioley
Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i...
2018: Frontiers in Immunology
Laura Tiberio, Annalisa Del Prete, Tiziana Schioppa, Francesca Sozio, Daniela Bosisio, Silvano Sozzani
Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for the development of immune tolerance. Immature DCs reside in peripheral tissues and specialize in antigen capture, whereas mature DCs reside mostly in the secondary lymphoid organs where they act as antigen-presenting cells. The correct localization of DCs is strictly regulated by a large variety of chemotactic and nonchemotactic signals that include bacterial products, DAMPs (danger-associated molecular patterns), complement proteins, lipids, and chemokines...
March 21, 2018: Cellular & Molecular Immunology
Lorraine A O'Reilly, Tracy L Putoczki, Lisa A Mielke, Jun T Low, Ann Lin, Adele Preaudet, Marco J Herold, Kelvin Yaprianto, Lin Tai, Andrew Kueh, Guido Pacini, Richard L Ferrero, Raffi Gugasyan, Yifang Hu, Michael Christie, Stephen Wilcox, Raelene Grumont, Michael D W Griffin, Liam O'Connor, Gordon K Smyth, Mathias Ernst, Paul Waring, Steve Gerondakis, Andreas Strasser
Polymorphisms in NFKB1 that diminish its expression have been linked to human inflammatory diseases and increased risk for epithelial cancers. The underlying mechanisms are unknown, and the link is perplexing given that NF-κB signaling reportedly typically exerts pro-tumorigenic activity. Here we have shown that NF-κB1 deficiency, even loss of a single allele, resulted in spontaneous invasive gastric cancer (GC) in mice that mirrored the histopathological progression of human intestinal-type gastric adenocarcinoma...
March 20, 2018: Immunity
Benjamin J Wolf, Jiyoung Elizabeth Choi, Mark A Exley
iNKT cells are a subset of innate-like T cells that utilize an invariant TCR alpha chain complexed with a limited repertoire of TCR beta chains to recognize specific lipid antigens presented by CD1d molecules. Because iNKT cells have an invariant TCR, they can be easily identified and targeted in both humans and mice via standard reagents, making this a population of T cells that has been well characterized. iNKT cells are some of the first cells to respond during an infection. By making different types of cytokines in response to different infection stimuli, iNKT cells help determine what kind of immune response then develops...
2018: Frontiers in Immunology
Luc Teyton
Research to connect lipids with immunology is growing, but details about the specific roles of lipid transfer proteins in antigen presentation remain unclear. A single class of major histocompatibility class-like molecules, called CD1 molecules, can present lipids and glycolipids to the immune system. These molecules all have a common hydrophobic antigen-binding groove. The loading of this groove with various lipids throughout the life of a CD1 molecule defines the immune recognition of lipids by T cells. At each location of residence, CD1 molecules are exposed to particular physico-chemical conditions, particular collections of lipids, and unique combinations of lipid transfer proteins that will define which lipid binds to CD1 and which do not...
March 19, 2018: Journal of Lipid Research
Shinji Yamada, Shunsuke Itai, Mika K Kaneko, Yukinari Kato
Programmed cell death-ligand 1 (PD-L1), which is a ligand of programmed cell death-1 (PD-1), is a type I transmembrane glycoprotein that is expressed on antigen-presenting cells and several tumor cells, including melanoma and lung cancer cells. There is a strong correlation between human PD-L1 (hPD-L1) expression on tumor cells and negative prognosis in cancer patients. In this study, we produced a novel anti-hPD-L1 monoclonal antibody (mAb), L1 Mab-4 (IgG2b , kappa), using cell-based immunization and screening (CBIS) method and investigated hPD-L1 expression in oral cancers...
March 2018: Biochemistry and Biophysics Reports
Rachel V Jimenez, Tyler T Wright, Nicholas R Jones, Jianming Wu, Andrew W Gibson, Alexander J Szalai
C-reactive protein (CRP) is the prototypical acute phase reactant, increasing in blood concentration rapidly and several-fold in response to inflammation. Recent evidence indicates that CRP has an important physiological role even at low, baseline levels, or in the absence of overt inflammation. For example, we have shown that human CRP inhibits the progression of experimental autoimmune encephalomyelitis (EAE) in CRP transgenic mice by shifting CD4+ T cells away from the TH 1 and toward the TH 2 subset. Notably, this action required the inhibitory Fcγ receptor IIB (FcγRIIB), but did not require high levels of human CRP...
2018: Frontiers in Immunology
Matteo Ugolini, Jenny Gerhard, Sanne Burkert, Kristoffer Jarlov Jensen, Philipp Georg, Friederike Ebner, Sarah M Volkers, Shruthi Thada, Kristina Dietert, Laura Bauer, Alexander Schäfer, Elisa T Helbig, Bastian Opitz, Florian Kurth, Saubashya Sur, Nickel Dittrich, Sumanlatha Gaddam, Melanie L Conrad, Christine S Benn, Ulrike Blohm, Achim D Gruber, Andreas Hutloff, Susanne Hartmann, Mark V Boekschoten, Michael Müller, Gregers Jungersen, Ralf R Schumann, Norbert Suttorp, Leif E Sander
Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation...
March 19, 2018: Nature Immunology
Mark Anczurowski, Yuki Yamashita, Munehide Nakatsugawa, Toshiki Ochi, Yuki Kagoya, Tingxi Guo, Chung-Hsi Wang, Muhammed A Rahman, Kayoko Saso, Marcus O Butler, Naoto Hirano
While the principles of classical antigen presentation via MHC class II are well-established, the mechanisms for the many routes of cross-presentation by which endogenous antigens become associated with class II molecules are not fully understood. We have recently demonstrated that the single amino acid polymorphism HLA-DPβ84Gly (DP84Gly ) is critical to abrogate class II invariant chain associated peptide (CLIP) region-mediated binding of invariant chain (Ii) to DP, allowing endoplasmic reticulum (ER)-resident endogenous antigens to constitutively associate with DP84Gly such as DP4...
March 19, 2018: Scientific Reports
Sandra Vreman, Gael Auray, Huub F J Savelkoul, Annemarie Rebel, Artur Summerfield, Norbert Stockhofe-Zurwieden
The present study investigated the innate immune response in vitro to determine porcine neonate responses with Toll-like receptor (TLR)2 ligand (Pam3Cys) or TLR9 ligand (CpG) and compare these with adults. We identified the same phenotypically defined dendritic cells (DC) subsets and DC proportions in porcine neonate and adult blood by flow cytometry, which were plasmacytoid DCs (pDCs): CD14- CD4+ CD172a+ CADM1- ) and conventional DCs (cDCs), the latter being further divided into a cDC1 (CD14- CD4- CD172alow CADM1+ ) and a cDC2 (CD14- CD4- CD172a+ CADM1+ ) subset...
March 16, 2018: Developmental and Comparative Immunology
Tuan Hiep Tran, Thi Thu Phuong Tran, Hanh Thuy Nguyen, Cao Dai Phung, Jee-Heon Jeong, Martina H Stenzel, Sung Giu Jin, Chul Soon Yong, Duy Hieu Truong, Jong Oh Kim
Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially cancer, which is the leading cause of mortality worldwide. Dendritic cells-the key antigen-presenting cells-play a pivotal role in immunological response by presenting exogenous epitopes to T cells, which induces the self-defense mechanisms of the body. Furthermore, nanotechnology has provided promising ways for diagnosing and treating cancer in the last decade...
March 16, 2018: International Journal of Pharmaceutics
Hui Liu, Zhenghu Jia, Chengmao Yang, Mei Song, Zhe Jing, Yapu Zhao, Zhenzhou Wu, Liqing Zhao, Dongsheng Wei, Zhinan Yin, Zhangyong Hong
Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic infectious diseases and cancers for not being able to induce cell-mediated (Th1) immunity. Here, we encapsulated an Alum colloid inside β-glucan particles (GPs), which are a type of natural particles derived from the yeast glucan shells, to prepare hybrid GP-Alum (GP-Al) adjuvant particles with a very uniform size of 2-4 μm. These hybrid particles can be used to load antigen proteins through a simple mixing procedure, and can be highly specifically targeted to antigen-presenting cells (APCs) and strongly activate dendritic cells (DCs) maturation and cytokine secretion...
March 12, 2018: Biomaterials
Yukio Fujiwara, Yoichi Saito, Takuya Shiota, Pan Cheng, Tsuyoshi Ikeda, Koji Ohnishi, Motohiro Takeya, Yoshihiro Komohara
Recent progress in anti-tumor therapy has revealed the significance of anti-tumor immune responses in tumor progression and clinical course in several kinds of malignant tumors. The draining lymph node is an important immune system component that contains a number of antigen-presenting cells, which induce rapid immune responses to foreign antigens. Current studies have shown that higher expression of CD169 on lymph node sinus macrophages is associated with the induction of anti-tumor immunity. In the present study, we searched for natural compounds that regulate the CD169-positive phenotype in macrophages to identify potential new anti-cancer agents targeting macrophage activation...
2018: Journal of Clinical and Experimental Hematopathology: JCEH
E Ridolo, I Martignago, S Masieri
Allergic Rhinitis (AR) is an IgE-mediated hypersensitivity disease caused by inhalation of an allergen to which the patients is sensitized. Etiopathogenesis of AR comprises a sensitization phase, an immediate phase and a late phase. In the sensitization phase, inhaled allergens are processed in peptides and come into contact with the nasal mucosa cells. Antigen-Presenting Cells (APCs), especially represented by Dendritic Cells (DCs), capture them through the interaction with their own MHC class II complexes and migrate to lymph nodes...
January 2018: Journal of Biological Regulators and Homeostatic Agents
Zilong Hu, Yue Ma, Zhiyang Shang, Shidong Hu, Kai Liang, Wentao Liang, Xiaowei Xing, Yufeng Wang, Xiaohui Du
Monoclonal antibodies recognizing programmed death-ligand 1 (PD-L1) have been used for the clinical treatment of diverse tumor types as a form of immune checkpoint inhibitor, with a favorable therapeutic effect. Dendritic cells (DCs) are potent antigen-presenting cells that serve a pivotal role in the activation of T cells, particularly cytotoxic T lymphocytes (CTLs). DC vaccines loaded with tumor antigens, DC-CTLs and activated T cells have been revealed to be a safe and effective treatment approach against colorectal cancer within a clinical setting...
April 2018: Oncology Letters
Stephanie Ascough, Suzanna Paterson, Christopher Chiu
Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived...
2018: Frontiers in Immunology
Camila Rubio-Patiño, Jozef P Bossowski, Gian Marco De Donatis, Laura Mondragón, Elodie Villa, Lazaro E Aira, Johanna Chiche, Rana Mhaidly, Cynthia Lebeaupin, Sandrine Marchetti, Konstantinos Voutetakis, Aristotelis Chatziioannou, Florence A Castelli, Patricia Lamourette, Emeline Chu-Van, François Fenaille, Tony Avril, Thierry Passeron, John B Patterson, Els Verhoeyen, Béatrice Bailly-Maitre, Eric Chevet, Jean-Ehrland Ricci
Dietary restriction (DR) was shown to impact on tumor growth with very variable effects depending on the cancer type. However, how DR limits cancer progression remains largely unknown. Here, we demonstrate that feeding mice a low-protein (Low PROT) isocaloric diet but not a low-carbohydrate (Low CHO) diet reduced tumor growth in three independent mouse cancer models. Surprisingly, this effect relies on anticancer immunosurveillance, as depleting CD8+ T cells, antigen-presenting cells (APCs), or using immunodeficient mice prevented the beneficial effect of the diet...
March 1, 2018: Cell Metabolism
Laura Santambrogio
This review will highlight our current understanding of the formation, circulation, and immunological role of lymphatic fluid. The formation of the extracellular fluid depends on the net balance between the hydrostatic and osmotic pressure gradients effective in the capillary beds. Lymph originates from the extracellular fluid and its composition combines the ultrafiltrated plasma proteins with the proteome generated by the metabolic activities of each parenchymal tissue. Several analyses have indicated how the lymph composition reflects the organs' physiological and pathological states...
2018: International Review of Cell and Molecular Biology
K M Okoniewska, A E Kedzierska, J Okoniewski, A Slawek, K Grzymajlo, A Chelmonska-Soyta, T Grabowski
Epitopes of regulatory T cells (tregitopes) represent linear sequences of amino acids that induce CD4+ CD25+ Foxp3+ T lymphocytes expansion both in vitro and in vivo. The tregitopes' effectiveness was confirmed in autoimmune disease mouse models and in murine transplant models. Therefore, tregitopes together with regulatory T cells (Tregs) could play a major role in maintaining immune tolerance. The purpose of the presented study was a selection of potential tregitopes and assessment of their impact on Tregs expansion...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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