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Nicholas Glanville, Tamlyn J Peel, Armin Schröder, Julia Aniscenko, Ross P Walton, Susetta Finotto, Sebastian L Johnston
Current understanding of adaptive immune, particularly T cell, responses to human rhinoviruses (RV) is limited. Memory T cells are thought to be of a primarily T helper 1 type, but both T helper 1 and T helper 2 memory cells have been described, and heightened T helper 2/ lessened T helper 1 responses have been associated with increased RV-induced asthma exacerbation severity. We examined the contribution of T helper 1 cells to RV-induced airways inflammation using mice deficient in the transcription factor T-Box Expressed In T Cells (Tbet), a critical controller of T helper 1 cell differentiation...
September 2016: PLoS Pathogens
Sandra Hoegl, Heidi Ehrentraut, Kelley S Brodsky, Francisco Victorino, Lucy Golden-Mason, Holger K Eltzschig, Eóin N McNamee
A critical step in the pathogenesis of acute lung injury (ALI) is excessive recruitment of polymorphonuclear neutrophils (PMNs) into the lungs, causing significant collateral tissue damage. Defining the molecular and cellular steps that control neutrophil infiltration and activation during ALI is therefore of important therapeutic relevance. Based on previous findings implicating the transcription factor Tbet in mucosal Th1-inflammation, we hypothesized a detrimental role for Tbet during ALI. In line with our hypothesis, initial studies of endotoxin-induced lung injury revealed a marked protection of Tbet(-/-) mice, including attenuated neutrophilia compared to WT counterparts...
September 6, 2016: Journal of Leukocyte Biology
Alper Tunga Özdemir, Rabia Bilge Özgül Özdemir, Cengiz Kırmaz, Ayla Eker Sarıboyacı, Zehra Seda Ünal Halbutoğlları, Ceren Özel, Erdal Karaöz
Mesenchymal stem cells (MSCs) have strong immunomodulatory properties, however these properties may show some differences according to the tissue type of their isolate. In this study we investigated the paracrine interactions between human DP derived MSCs (hDP-MSCs) and the CD4(+) T helper cell subsets to establish their immunomodulatory mechanisms. We found that the CD4(+)-Tbet(+) (Th1) and CD4(+)-Gata3(+) (Th2) cells were suppressed by the hDP-MSCs, but the CD4(+)-Stat3(+) (Th17) and CD4(+)-CD25(+)-FoxP3(+) (Treg) cells were stimulated...
August 24, 2016: Cellular Immunology
Hong-Wen Liu, Xiaoyan Zhu, Jing Zhang, Xiao-Bing Zhang, Weihong Tan
Cellular self-regulation of reactive oxygen species (ROS) stress via antioxidant repair plays an important role in maintaining the redox balance. The redox balance between reducing and oxidizing species within cells is significant in the regulation of a signal pathway and is achieved by a series of elaborate mechanisms. In this work, we employed our previously reported D-π-A-structured naphthalene-BODIPY TBET platform to design an efficient two-photon fluorescent probe for dynamic monitoring of superoxide anion oxidative stress and the GSH reducing repair process...
October 21, 2016: Analyst
Leo Swadling, John Halliday, Christabel Kelly, Anthony Brown, Stefania Capone, M Azim Ansari, David Bonsall, Rachel Richardson, Felicity Hartnell, Jane Collier, Virginia Ammendola, Mariarosaria Del Sorbo, Annette Von Delft, Cinzia Traboni, Adrian V S Hill, Stefano Colloca, Alfredo Nicosia, Riccardo Cortese, Paul Klenerman, Antonella Folgori, Eleanor Barnes
An effective therapeutic vaccine for the treatment of chronic hepatitis C virus (HCV) infection, as an adjunct to newly developed directly-acting antivirals (DAA), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic HCV infection. A recombinant chimpanzee adenoviral (ChAd3) vector and a modified vaccinia Ankara (MVA), encoding the non-structural proteins of HCV (NSmut), used in a heterologous prime/boost regimen induced multi-specific, high-magnitude, durable HCV-specific CD4+ and CD8+ T-cell responses in healthy volunteers, and was more immunogenic than a heterologous Ad regimen...
August 2, 2016: Vaccines
Sharee A Basdeo, Siobhan Kelly, Karen O'Connell, Niall Tubridy, Christopher McGuigan, Jean M Fletcher
BACKGROUND: The ability to identify clinically isolated syndrome (CIS) patients at high risk of progression to clinically definite multiple sclerosis (CDMS) would be clinically beneficial. The initiation of T cell mediated autoimmune diseases such as multiple sclerosis (MS) requires the initial inappropriate activation and differentiation of auto-reactive CD4(+) T cells. The quiescence of naive T cells is actively maintained by molecules such as TOB1, which control the threshold of activation...
2016: SpringerPlus
Mohammad Nizam Uddin, Dil Afroz Sultana, Kyle J Lorentsen, Jonathan J Cho, Mariana E Kirst, Mark L Brantly, Danielle Califano, Derek B Sant'Angelo, Dorina Avram
Invariant natural killer T (iNKT) cells are innate-like T cells that recognize glycolipid antigens and play critical roles in regulation of immune responses. Based on expression of the transcription factors (TFs) Tbet, Plzf, and Rorγt, iNKT cells have been classified in effector subsets that emerge in the thymus, namely, iNKT1, iNKT2, and iNKT17. Deficiency in the TF Bcl11b in double-positive (DP) thymocytes has been shown to cause absence of iNKT cells in the thymus and periphery due to defective self glycolipid processing and presentation by DP thymocytes and undefined intrinsic alterations in iNKT precursors...
July 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Nora Zulehner, Birgit Nagl, Peter Briza, Anargyros Roulias, Barbara Ballmer-Weber, Gerhard Johann Zlabinger, Fatima Ferreira, Barbara Bohle
BACKGROUND: In contrast to other Bet v 1-related food allergens, the major carrot allergen, Dau c 1, has been suggested to induce food allergy independently from Bet v 1. As T cells are crucial in the sensitization process we sought to characterize the T cell response to Dau c 1 and its cross-reactivity with Bet v 1. METHODS: Dau c 1-specific T cell lines (TCL) and clones (TCC) established from PBMC of birch pollen-allergic patients with carrot allergy were analyzed for reactivity to Bet v 1, epitope-specificity, allergen-induced cytokine secretion and expression of integrins α4β7 and α4β1, critical for gut and lung homing, respectively...
May 25, 2016: Allergy
Matthew W Rosenbaum, Jacob R Bledsoe, Vicente Morales-Oyarvide, Tiffany G Huynh, Mari Mino-Kenudson
Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key suppressors of the cytotoxic immune response. PD-L1 expression on tumor cells may be induced by the immune microenvironment, resulting in immune escape (adaptive immune resistance), and an adverse prognosis in many malignancies. In colorectal carcinoma the response to PD-1/PD-L1 inhibition is correlated with microsatellite instability. However, little is known about the clinicopathologic, molecular, and prognostic characteristics of colorectal carcinoma with PD-L1 expression...
September 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Verena Brucklacher-Waldert, Cristina Ferreira, Silvia Innocentin, Shraddha Kamdar, David R Withers, Marika C Kullberg, Marc Veldhoen
The discovery of Th17 cell plasticity, in which CD4(+) IL-17-producing Th17 cells give rise to IL-17/IFN-γ double-producing cells and Th1-like IFNγ(+) ex-Th17 lymphocytes, has raised questions regarding which of these cell types contribute to immunopathology during inflammatory diseases. In this study, we show using Helicobacter hepaticus-induced intestinal inflammation that IL-17A(Cre)- or Rag1(Cre)-mediated deletion of Tbx21 has no effect on the generation of IL-17/IFN-γ double-producing cells, but leads to a marked absence of Th1-like IFNγ(+) ex-Th17 cells...
June 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Yu-Jin Zhang, Xin Wang, Yong Zhou, Chuan-Kui Wang
Optical properties of a series of molecular two-photon fluorescent Cu(2+) probes containing the same acceptor (rhodamine group) are analyzed using time-dependent density functional theory in combination with analytical response theory. Special emphasis is placed on evolution of the probes' optical properties in the presence of Cu(2+) . In this study, the compound with naphthalene as the donor is shown to be excellent ratiometric fluorescent chemosensor, whereas the compound with quinoline derivative as the donor shows off/on-typed colorimetric fluorescent response...
July 2016: Photochemistry and Photobiology
Audrey Hennequin, Valentin Derangère, Romain Boidot, Lionel Apetoh, Julie Vincent, David Orry, Jean Fraisse, Sylvain Causeret, François Martin, Laurent Arnould, Françoise Beltjens, François Ghiringhelli, Sylvain Ladoire
Tumor-infiltrating T and B lymphocytes could have the potential to affect cancer prognosis. The objective of this study was to investigate the prognostic significance of tumor infiltration by CD8 and CD4 T cells, and B lymphocytes in patients with localized gastric cancer. In a retrospective cohort of 82 patients with localized gastric cancer and treated by surgery we quantitatively assessed by immunohistochemistry on surgical specimen, immune infiltrates of IL-17(+), CD8(+), Foxp3(+), Tbet(+) T cells and CD20(+) B cells both in the tumor core and at the invasive margin via immunohistochemical analyses of surgical specimens...
February 2016: Oncoimmunology
Jin Lee, Matthew Machin, Kirsty E Russell, Stelios Pavlidis, Jie Zhu, Peter J Barnes, Kian F Chung, Ian M Adcock, Andrew L Durham
We investigated changes in gene expression that occur in chronic obstructive pulmonary disease (COPD) after corticosteroid treatment and sought to identify the mechanisms that regulate these changes. Biopsy samples were taken from patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage I to II) before and after treatment with fluticasone propionate (FP)/salmeterol (SM) (50/500, 4 wk). Gene expression was measured by microarray and was confirmed by real-time reverse transcription-quantitative PCR (RT-qPCR)...
May 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Martin H Stradner, Kitty P Cheung, Anna Lasorella, Ananda W Goldrath, Louise M D'Cruz
While the invariant natural killer T (iNKT)-cell response to primary stimulation with the glycolipid, α-galactosylceramide (αGalCer), is robust, the secondary response to this stimulus is muted resulting in a hyporesponsive state characterized by anti-inflammatory interleukin-10 (IL-10) production and high expression of programmed cell death 1 (PD1) and neuropilin 1 (NRP1). The E protein transcription factors and their negative regulators, the Id proteins, have previously been shown to regulate iNKT cell thymic development, subset differentiation and peripheral survival...
August 2016: Immunology and Cell Biology
Esther Leal, Aitor G Granja, Carlos Zarza, Carolina Tafalla
Although the skin constitutes the first line of defense against waterborne pathogens, there is a great lack of information regarding the skin associated lymphoid tissue (SALT) and whether immune components of the skin are homogeneously distributed through the surface of the fish is still unknown. In the current work, we have analyzed the transcription of several immune genes throughout different rainbow trout (Oncorhynchus mykiss) skin areas. We found that immunoglobulin and chemokine gene transcription levels were higher in a skin area close to the gills...
2016: PloS One
Xiang Han, Lei Zhao, Dong-En Wang, Juan Xu, Longlong Zhang, Mao-Sen Yuan, Qin Tu, Jinyi Wang
In this paper, we designed and synthesized a novel TBET-based ratiometric fluorescent chemodosimeter, RH-Au, for Au(3+). It was found that the probe RH-Au displayed highly selective, sensitive and naked-eye detection upon the addition of Au(3+). The probe RH-Au can be used in the pH range 6.0-7.5 and the detection limit was determined to be as low as 2.91 nM (0.57 ppb). We also demonstrated a successful application of imaging Au(3+) in living cells using RH-Au.
February 7, 2016: Analyst
Huiqing Hou, Runjing Cao, Jun Miao, Yafei Sun, Xiaoqian Liu, Xiujuan Song, Li Guo
Fingolimod is a new immunosuppressive agent approved by Food and Drug Administration (FDA) for treating multiple sclerosis (MS). It acts as a functional antagonist to downregulate the S1P1 receptor, which is known to signal through the Akt-mTOR pathway. We investigated the mechanism of fingolimod action in the classical animal model of MS: experimental autoimmune encephalomyelitis (EAE). Fingolimod treatment significantly reduced clinical scores and histopathology in this model, even when treatment was begun after the onset of pathology...
January 2016: International Immunopharmacology
Volker Daniel, Karina Trojan, Gerhard Opelz
BACKGROUND: We reported previously that patients with poor long-term graft function are able to form IFNy+ Treg in vitro pretransplant, but late posttransplant have more frequently undetectable or lower levels of IFNy+ Treg in the peripheral blood than patients with good long-term graft outcome. In the present study, we investigated the induction of IFNy+ and Tbet+ Treg subsets in the presence of immunosuppressants in vitro. METHODS: PBL of 10 healthy individuals were stimulated with PMA/Ionomycin in the presence of different immunosuppressive drugs at 2 different concentrations that were chosen to approximately mirror the blood levels in renal transplant recipients...
January 2016: Human Immunology
Yan-Ru Zhang, Ning Meng, Jun-Ying Miao, Bao-Xiang Zhao
A simple ratiometric probe (Naph-Rh) has been designed and synthesized based on a through-bond energy transfer (TBET) system for sensing HOCl. In this probe, rhodamine thiohydrazide and naphthalene formyl were connected by simple synthesis methods to construct a structure of monothio-bishydrazide. Free probe Naph-Rh showed only the emission of naphthalene. When probe Naph-Rh reacted with HOCl, monothio-bishydrazide could be converted into 1,2,4-oxadiazole, which not only ensured that the donor and the acceptor were connected with electronically conjugated bonds, but also resulted in the spiro-ring opening and the emission of rhodamine...
December 21, 2015: Chemistry: a European Journal
Judith H Aberle, Julia Schwaiger, Stephan W Aberle, Karin Stiasny, Ondrej Scheinost, Michael Kundi, Vaclav Chmelik, Franz X Heinz
Tick-borne encephalitis virus (TBEV) is a human-pathogenic flavivirus that is endemic in large parts of Europe and Asia and causes severe neuroinvasive illness. A formalin-inactivated vaccine induces strong neutralizing antibody responses and confers protection from TBE disease. CD4+ T cell responses are essential for neutralizing antibody production, but data on the functionalities of TBEV-specific CD4+ T cells in response to vaccination or infection are lacking. This study provides a comprehensive analysis of the cytokine patterns of CD4+ T cell responses in 20 humans after TBE vaccination in comparison to those in 18 patients with TBEV infection...
2015: PloS One
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