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Th1 cells

Liang Cheng, Fan Yang, Xin Cao, Guo-Qing Li, Ting-Ting Lu, Yun-Qing Zhu, Yun Hu, Xiao-Ming Mao
AIMS: To evaluate the effect of short-term intensive insulin therapy on circulating T cell subpopulations in patients with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS: A total of 113 patients with T2DM and 28 normal subjects were enrolled. Demographic parameters and biochemical markers were collected at baseline, and flow cytometry was applied to determine the proportion of T cell subpopulations in participants. Then the patients underwent continuous subcutaneous insulin injection (CSII) treatment with euglycemia for 2 weeks, and the T cell subpopulations were measured again after CSII treatment...
February 10, 2019: Diabetes Research and Clinical Practice
Henk-Jan van den Ham, Nadine A Binai, Fatiha Zaaraoui-Boutahar, Albert J R Heck, Arno C Andeweg
Helper T cell differentiation is a key process in the regulation of adaptive immune responses. Here, we profile mouse Th1 and Th2 cells using high-throughput proteomics to increase our understanding of the molecular biology of Th differentiation to support the design of prophylactic and therapeutic intervention strategies for (infectious) diseases. Protein profiling of Th1/Th2 differentiated cells resulted in the quantification of almost 6000 proteins of which 41 were differentially expressed at FDR < 0...
February 13, 2019: Proteomics
Anna Lysén, Ranveig Braathen, Arnar Gudjonsson, Demo Yemane Tesfaye, Bjarne Bogen, Even Fossum
Fusing antigens to chemokines to target antigen presenting cells (APC) is a promising method for enhancing immunogenicity of DNA vaccines. However, it is unclear how different chemokines compare in terms of immune potentiating effects. Here we compare Ccl3- and Xcl1-fusion vaccines containing hemagglutinin (HA) from influenza A delivered by intramuscular (i.m.) or intradermal (i.d.) DNA vaccination. Xcl1 fusion vaccines target cDC1s, and enhance proliferation of CD4+ and CD8+ T cells in vitro. In contrast, Ccl3 target both cDC1 and cDC2, but only enhance CD4+ T cell proliferation in combination with cDC2...
February 12, 2019: Scientific Reports
Denis Migliorini, Valérie Dutoit, Mathilde Allard, Nicole Grandjean Hallez, Eliana Marinari, Valérie Widmer, Géraldine Philippin, Francesca Corlazzoli, Robin Gustave, Mario Kreutzfeldt, Nathalie Blazek, Joëlle Wasem, Andreas Hottinger, Avinash Koka, Shahan Momjian, Alexander Lobrinus, Doron Merkler, Maria-Isabel Vargas, Paul R Walker, Anna Patrikidou, Pierre-Yves Dietrich
Background: Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC in HLA-A2 + glioma patients. Methods: Adult patients with newly diagnosed glioblastoma (n=16) and grade III astrocytoma (n=3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination...
February 12, 2019: Neuro-oncology
Christoph M Griessinger, Andreas M Schmid, Dominik Sonanini, Barbara F Schörg, Mohamed Ali Jarboui, Daniel Bukala, Natalie Mucha, Birgit Fehrenbacher, Julia Steinhilber, Manuela Martella, Ursula Kohlhofer, Martin Schaller, Lars Zender, Hans-Georg Rammensee, Leticia Quintanilla-Martinez, Martin Röcken, Manfred Kneilling, Bernd J Pichler
Cancer treatment with adoptively transferred tumor-associated antigen-specific CD4+ T-helper cells is a promising immunotherapeutic approach. In the pancreatic cancer model RIP-Tag2, the intraperitoneal (i.p.) application of Tag-specific TH1 cells exhibited a profound antitumoral efficiency. We investigated, whether an intravenous (i.v.) application of Tag-TH1 cells induces an equivalent therapeutic effect. Adoptively transferred fluorescent Tag-TH1 cells revealed a pronounced homing to the tumors after either i...
February 7, 2019: Carcinogenesis
R Barroso-Sousa, W T Barry, H Guo, D Dillon, Y B Tan, K Fuhrman, W Osmani, A Getz, M Baltay, C Dang, D Yardley, B Moy, P K Marcom, E A Mittendorf, I E Krop, E P Winer, S M Tolaney
Background: Previous data suggest that the immune microenvironment plays a critical role in HER2-positive breast cancer, however there is little known about the immune profiles of small HER2-positive tumors. In this study we aimed to characterize the immune microenvironment of small HER2-positive breast cancers included in the APT trial, and to correlate the immune markers with pathological and molecular tumor characteristics. Patients and Methods: The APT trial was a multicenter, single-arm phase II study of paclitaxel and trastuzumab in patients with node-negative HER2-positive breast cancer...
February 7, 2019: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Katelyn Paz, Ryan Flynn, Jing Du, Stacey Tannheimer, Amy J Johnson, Shuai Dong, Anne-Katrien Stark, Klaus Okkenhaug, Angela Panoskaltsis-Mortari, Peter T Sage, Arlene H Sharpe, Leo Luznik, Jerome Ritz, Robert J Soiffer, Corey S Cutler, John Koreth, Joseph H Antin, David B Miklos, Kelli P MacDonald, Geoffrey R Hill, Ivan Maillard, Jonathan S Serody, William J Murphy, David H Munn, Colby Feser, Michael Zaiken, Bart Vanhaesebroeck, Laurence A Turka, John C Byrd, Bruce R Blazar
Chronic graft-versus-host disease is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T-cells can differentiate into pathogenic T helper (Th)-17 cells and germinal center -promoting Tfollicular helper cells, resulting in cGVHD. Phosphoinositide-3-kinase-δ, a lipid kinase, is critical for activated T-cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3Kδ activity in donor T-cells that become Tfhs is required for cGVHD in a non-sclerodermatous multi-organ system disease model that includes bronchiolitis obliterans, dependent upon GC B-cells, Tfhs, and counterbalanced by Tfollicular regulatory cells, each requiring PI3Kδ signaling for function and survival...
February 12, 2019: American Journal of Transplantation
Hitoshi Tajima, Risako Tajiki-Nishino, Yuko Watanabe, Tomoki Fukuyama
The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that binds to various environmental chemicals and contributes to numerous toxicological effects. However, the direct effects of AhR on the development of allergic diseases are not fully understood. The main aim of this study was to elucidate the action of AhR in the development of cutaneous allergies. Initially, the potential for a direct relationship between AhR and the immune cells was investigated in vitro, using murine bone marrow-derived dendritic cells, human epidermal keratinocytes, and the mixed leukocyte reaction assay...
February 12, 2019: Journal of Applied Toxicology: JAT
Alex B Blair, Jennifer Kleponis, Dwayne L Thomas Ii, Stephen T Muth, Adrian G Murphy, Victoria Kim, Lei Zheng
Pancreatic ductal adenocarcinoma (PDAC) represents an immune quiescent tumor that is resistant to immune checkpoint inhibitors. Previously, our group has shown that a GM-CSF secreting allogenic pancreatic tumor cell vaccine (GVAX), may prime the tumor microenvironment by inducing intratumoral T-cell infiltration. Here, we show that untreated PDACs express minimal indoleamine-2, 3-dioxygenase (IDO1); however, GVAX therapy induced IDO1 expression on tumor epithelia as well as vaccine-induced tertiary lymphoid aggregates...
February 12, 2019: Journal of Clinical Investigation
Giuliana Guggino, Claudia Schinocca, Marianna Lo Pizzo, Diana Di Liberto, Domenico Garbo, Stefania Raimondo, Riccardo Alessandro, Filippo Brighina, Piero Ruscitti, Roberto Giacomelli, Guido Sireci, Giovanni Triolo, Roberto Casale, Piercarlo Sarzi-Puttini, Francesco Dieli
OBJECTIVES: Hyperbaric oxygen therapy (HBOT) has been used as treatment for different clinical conditions, including fibromyalgia (FM). HBOT modulates brain activity, ameliorates chronic pain and modifies the ratio of immune cells. Clinical studies have provided evidence that FM is associated with immune system dysregulation. In the present study we aimed to evaluate the effect of HBOT on immune system and on the quality of life-style of FM patients. METHODS: Patients with primary FM and controls were treated with HBOT...
January 2019: Clinical and Experimental Rheumatology
Siew-Kim Khoo, James Read, Kimberley Franks, Guicheng Zhang, Joelene Bizzintino, Laura Coleman, Christopher McCrae, Lisa Öberg, Niamh M Troy, Franciska Prastanti, Janet Everard, Stephen Oo, Meredith L Borland, Rose A Maciewicz, Peter N Le Souëf, Ingrid A Laing, Anthony Bosco
Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7hi versus IRF7lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Kahina Amrouche, Jacques-Olivier Pers, Christophe Jamin
The control of the activities of regulatory B (Breg) cells in immune disorders is an emerging therapeutic strategy for the recovery of immune homeostasis. Manipulating B cells using numerous drugs in vivo affect their regulatory functions, although a direct link has not yet been demonstrated. Glatiramer acetate (GA) is a synthetic polypeptide that is used in the treatment of inflammatory and autoimmune diseases. We experimented on an in vitro coculture system to determine its direct effects on the Breg cell properties of human B cells...
February 11, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Adam D Cohen, Nikoletta Lendvai, Sarah Nataraj, Naoko Imai, Achim A Jungbluth, Ioanna Tsakos, Adeeb Rahman, Anna Hc Mei, Herman Singh, Katarzyna Zarychta, Seunghee Kim-Schulze, Andrew J Park, Ralph R Venhaus, R Katherine Alpaugh, Sacha Gnjatic, Hearn Jay Cho
Autologous stem cell transplant (autoSCT), the standard consolidation therapy for multiple myeloma, improves disease-free survival but is not curative. This could be an ideal setting for immunologic therapy. However, the immune milieu is impaired after autoSCT. We hypothesized that autologous lymphocyte infusion would restore immune competence, allowing immunotherapies such as cancer vaccines to elicit tumor antigen-specific immunity in the setting of autoSCT. In this pilot study (NCT01380145), we investigated safety, immunologic, and clinical outcomes of autologous lymphocyte infusion combined with peri-autoSCT immunotherapy with recombinant MAGE-A3 (a multiple myeloma-associated antigen) and adjuvant...
February 11, 2019: Cancer Immunology Research
M Kardan, A Rafiei, J Ghafari, R Valadan, Z Morsaljahan, S T Haj-Ghorbani
INTRODUCTION AND OBJECTIVES: Allergic asthma is a chronic inflammatory disorder of the airways. Th1, Th2 and Th17 cells are the main cells involved in the pathophysiology of asthma. The function of these cells is affected by T-bet, GATA3 and RORγt transcription factors (respectively). Therefore, the aim of this study was to evaluate the effect of ginger (officinal Roscoe) extract on the expression of T-bet, GATA-3 and ROR-γ in peripheral blood mononuclear cells (PBMC) of asthmatic patients, in comparison with healthy volunteers as controls...
February 8, 2019: Allergologia et Immunopathologia
Alexandra Audemard-Verger, Evangéline Pillebout, Agnès Jamin, Laureline Berthelot, Cédric Aufray, Bruno Martin, Aurélie Sannier, Eric Daugas, Julie Déchanet-Merville, Yolande Richard, Renato Monteiro, Bruno Lucas
OBJECTIVES: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients. METHODS: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cytometry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by immunohistochemistry...
February 8, 2019: Journal of Autoimmunity
Zrinka Oreskovic, Katerina Nechvatalova, Josef Krejci, Vladimir Kummer, Martin Faldyna
Intradermal (i.d.) application of vaccine is promising way how to induce specific immune response against particular pathogens. Adjuvants, substances added into vaccination dose with the aim to increase immunogenicity, play important role in activation of dendritic cells with subsequent activation of lymphocytes. They can, however, induce unwanted local reactions. The aim of the study was to determine the effect of i.d. administration of model antigen keyhole limped hemocyanine alone or with different adjuvants-aluminium hydroxide and oil-based adjuvants-on local histopathological reaction as well as dendritic cell activation at the site of administration and local cytokine and chemokine response...
2019: PloS One
Jacquelyn A Gorman, Christian Hundhausen, Mackenzie Kinsman, Tanvi Arkatkar, Eric J Allenspach, Courtnee Clough, Samuel E West, Kerri Thomas, Ahmet Eken, Socheath Khim, Malika Hale, Mohamed Oukka, Shaun W Jackson, Karen Cerosaletti, Jane H Buckner, David J Rawlings
TYK2 is a JAK family member that functions downstream of multiple cytokine receptors. Genome wide association studies have linked a SNP (rs34536443) within TYK2 encoding a Proline to Alanine substitution at amino acid 1104, to protection from multiple autoimmune diseases including systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The protective role of this SNP in autoimmune pathogenesis, however, remains incompletely understood. Here we found that T follicular helper (Tfh) cells, switched memory B cells, and IFNAR signaling were decreased in healthy individuals that expressed the protective variant TYK2 A 1104 ( TYK2 P )...
2019: Frontiers in Immunology
Jian Deng, Xiao-Qiang Yu, Pei-Hui Wang
Immune sensing of exogenous molecules from microbes (e.g., pathogen-associated molecular patterns) and nonmicrobial molecules (e.g., asbestos, alum, and silica), as well as endogenous damage-associated molecular patterns (e.g., ATP, uric acid crystals, and amyloid A) activates innate immunity by inducing immune-related genes, including proinflammatory cytokines, which further facilitate the development of adaptive immunity. The roles of transcriptional responses downstream of immune sensing have been widely characterized in informing adaptive immunity; however, few studies focus on the effect of post-translational responses on the modulation of adaptive immune responses...
February 7, 2019: Molecular Immunology
Ellen K Wasan, Jaweria Syeda, Stacy Strom, Jacqueline Cawthray, Robert E Hancock, Kishor M Wasan, Volker Gerdts
We previously developed an highly efficacious combination adjuvant comprised of innate defense regulator (IDR)-1002 peptide, poly(I:C) and polyphosphazene (TriAdj). Here we aimed to design and test the in vivo efficacy of a mucoadhesive nasal formulation of this adjuvant. To determine the physical properties of the formulation, the effect of addition of each individual component was characterised by gel electrophoresis and fluorescence quenching using rhodamine-poly(I:C). Cationic liposomes comprised of didodecyl dimethylammonium bromide (DDAB), dioleoyl phosphatidylethanolamine (DOPE) (50:50 or 75:25 mol:mol) and DDAB, L-α-phosphatidylcholine (egg PC) and DOPE (40:50:10 mol:mol:mol) were prepared by the thin-film extrusion method...
February 7, 2019: Vaccine
Cecilia Graciela Giadans, Daniela Alejandra Ríos, Beatriz Ameigeiras, Adriana Mónica Pietrantonio, Néstor Lucio Lucatelli, Leila Haddad, Eduardo Mullen, Fabiana Heinrich, Elena De Matteo, Diego Flichman, Pamela Valva, María Victoria Preciado
In Chronic Hepatitis B (CHB) infection, virus and immune response interplay is thought to be responsible for pathogenesis. Yet, the impact of each immune cell population and viral protein expression in liver damage is still unknown. Our aim was to study the interplay between intrahepatic immune response and viral activity in relation to CHB liver damage. Immunostaining was performed in 29 liver biopsies from untreated CHB patients to characterize liver infiltrate [Th (CD4+), CTL (CD8+), Treg (FoxP3+), Th17 (IL-17A+) and Th1 (Tbet+)] and viral antigen expression (HBsAg and HBcAg)...
February 9, 2019: Journal of Viral Hepatitis
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