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Costimulatory t cells

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https://www.readbyqxmd.com/read/28904313/immune-receptors-cd40-and-cd86-in-oral-keratinocytes-and-implications-for-oral-lichen-planus
#1
Alison Marshall, Antonio Celentano, Nicola Cirillo, Michiko Mirams, Michael McCullough, Stephen Porter
Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease that targets stratified epithelia, including those lining the oral cavity. The intraoral variant of LP (OLP) is associated with interferon (IFN)-γ production by infiltrating T lymphocytes; however, the role of epithelial cells in the etiopathogenesis OLP is not completely understood. There is however a growing body of evidence regarding the involvement of epithelial-derived cytokines, immune receptors, and costimulatory molecules in the pathobiological processes that promote and sustain OLP...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28901417/discrimination-of-the-heterogeneity-of-bone-marrow%C3%A2-derived-dendritic-cells
#2
Jing Wang, Xiaomin Dai, Chiaching Hsu, Changsheng Ming, Ying He, Ji Zhang, Lai Wei, Ping Zhou, Cong-Yi Wang, Jun Yang, Nianqiao Gong
The present study aimed to discriminate different subsets of cultured dendritic cells (DCs) to evaluate their immunological characteristics. DCs offer an important foundation for immunological studies, and mouse bone marrow (BM) cells cultured with granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) have been used extensively to generate CD11c+/major histocompatibility complex II+ BM‑derived DCs (BMDCs). Immature DCs are considered to have strong migration and phagocytic antigen‑capturing abilities, whereas mature DCs are thought to activate naive T cells and express high levels of costimulatory cytokines and adhesion molecules...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900681/regulatory-dendritic-cells
#3
Katsuaki Sato, Tomofumi Uto, Tomohiro Fukaya, Hideaki Takagi
Dendritic cells (DCs) comprise heterogeneous subsets, functionally classified into conventional DCs (cDCs) and plasmacytoid DCs (pDCs). DCs are considered to be essential antigen (Ag)-presenting cells (APCs) that play crucial roles in activation and fine-tuning of innate and adaptive immunity under inflammatory conditions, as well as induction of immune tolerance to maintain immune homeostasis under steady-state conditions. Furthermore, DC functions can be modified and influenced by stimulation with various extrinsic factors, such as ligands for pattern-recognition receptors (PRRs) and cytokines...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900679/ctla-4-an-essential-immune-checkpoint-for-t-cell-activation
#4
Shunsuke Chikuma
The response of peripheral T lymphocytes (T cell) is controlled by multiple checkpoints to avoid unwanted activation against self-tissues. Two opposing costimulatory receptors, CD28 and CTLA-4, on T cells bind to the same ligands (CD80 and CD86) on antigen-presenting cells (APCs), and provide positive and negative feedback for T-cell activation, respectively. Early studies suggested that CTLA-4 is induced on activated T cells and binds to CD80/CD86 with much stronger affinity than CD28, providing a competitive inhibition...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28900678/socs1-regulator-of-t-cells-in-autoimmunity-and-cancer
#5
Subburaj Ilangumaran, Diwakar Bobbala, Sheela Ramanathan
SOCS1 is a negative feedback regulator of cytokine and growth factor receptor signaling, and plays an indispensable role in attenuating interferon gamma signaling. Studies on SOCS1-deficient mice have established a crucial role for SOCS1 in regulating CD8(+) T cell homeostasis. In the thymus, SOCS1 prevents thymocytes that had failed positive selection from surviving and expanding, ensures negative selection and prevents inappropriate developmental skewing toward the CD8 lineage. In the periphery, SOCS1 not only controls production of T cell stimulatory cytokines but also attenuates the sensitivity of CD8(+) T cells to synergistic cytokine stimulation and antigen non-specific activation...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28895168/9-cis-retinoic-acid-induces-a-distinct-regulatory-dendritic-cell-phenotype-that-modulates-murine-delayed-type-allergy
#6
Lea-Franziska Kraus, Natalie Scheurmann, Denis F Frenzel, Alpaslan Tasdogan, Johannes M Weiss
BACKGROUND: Hand eczema, which is frequently caused by delayed-type allergy, is treated with 9-cis-retinoic acid (9cisRA). However, knowledge on how 9cisRA modulates skin immunity is sparse. OBJECTIVE: As dendritic cells (DCs) are central in the pathogenesis of contact allergy, we investigated 9cisRA modulation of DC function in murine contact hypersensitivity (CHS). METHODS: 9cisRA-differentiated DCs (9cisRA-DCs) were analysed for phenotype and function...
September 12, 2017: Contact Dermatitis
https://www.readbyqxmd.com/read/28878738/overlooked-mechanisms-in-type-1-diabetes-etiology-how-unique-costimulatory-molecules-contribute-to-diabetogenesis
#7
REVIEW
David H Wagner
Type 1 Diabetes (T1D) develops when immune cells invade the pancreatic islets resulting in loss of insulin production in beta cells. T cells have been proven to be central players in that process. What is surprising, however, is that classic mechanisms of tolerance cannot explain diabetogenesis; alternate mechanisms must now be considered. T cell receptor (TCR) revision is the process whereby T cells in the periphery alter TCR expression, outside the safety-net of thymic selection pressures. This process results in an expanded T cell repertoire, capable of responding to a universe of pathogens, but limitations are that increased risk for autoimmune disease development occurs...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28861075/ebola-virus-glycoprotein-induces-an-innate-immune-response-in-vivo-via-tlr4
#8
Chih-Yun Lai, Daniel P Strange, Teri Ann S Wong, Axel T Lehrer, Saguna Verma
Ebola virus (EBOV), a member of the Filoviridae family, causes the most severe form of viral hemorrhagic fever. Although no FDA licensed vaccine or treatment against Ebola virus disease (EVD) is currently available, Ebola virus glycoprotein (GP) is the major antigen used in all candidate Ebola vaccines. Recent reports of protection as quickly as within 6 days of administration of the rVSV-based vaccine expressing EBOV GP before robust humoral responses were generated suggests that the innate immune responses elicited early after vaccination may contribute to the protection...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28860806/enhancement-of-antitumor-activity-by-using-a-fully-human-gene-encoding-a-single-chain-fragmented-antibody-specific-for-carcinoembryonic-antigen
#9
Hirotomo Shibaguchi, Naixiang Luo, Naoto Shirasu, Motomu Kuroki, Masahide Kuroki
Human leukocyte antigen and/or costimulatory molecules are frequently lacking in metastatic tumor cells, and thus tumor cells are able to escape from the immune system. Although lymphocytes with a chimeric antigen receptor (CAR) is a promising approach for overcoming this challenge in cancer immunotherapy, administration of modified T cells alone often demonstrates little efficacy in patients. Therefore, in order to enhance the antitumor activity of immune cells in the cancer microenvironment, we used lymphocytes expressing CAR in combination with a fusion protein of IL-2 that contained the single-chain fragmented antibody (scFv) specific for the carcinoembryonic antigen...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28856237/t-cell-activating-mesenchymal-stem-cells-as-a-biotherapeutic-for-hcc
#10
Arpad Szoor, Abishek Vaidya, Mireya Paulina Velasquez, Zhuyong Mei, Daniel L Galvan, David Torres, Adrian Gee, Andras Heczey, Stephen Gottschalk
The outcome for advanced stage hepatocellular carcinoma (HCC) remains poor, highlighting the need for novel therapies. Genetically modified mesenchymal stem cells (MSCs) are actively being explored as cancer therapeutics due to their inherent ability to migrate to tumor sites. We reasoned that MSCs can be genetically modified to redirect T cells to Glypican-3 (GPC3)(+) HCC, and genetically modified these with viral vectors encoding a GPC3/CD3 bispecific T cell engager (GPC3-ENG), a bispecifc T cell engager specific for an irrelevant antigen (EGFRvIII), and/or costimulatory molecules (CD80 and 41BBL)...
September 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28855904/immunological-properties-of-murine-parthenogenetic-stem-cell-derived-cardiomyocytes-and-engineered-heart-muscle
#11
Michael Didié, Satish Galla, Vijayakumar Muppala, Ralf Dressel, Wolfram-Hubertus Zimmermann
Pluripotent parthenogenetic stem cells (pSCs) can be derived by pharmacological activation of unfertilized oocytes. Homozygosity of the major histocompatibility complex (MHC) in pSCs makes them an attractive cell source for applications in allogeneic tissue repair. This was recently demonstrated for pSC-based tissue-engineered heart repair. A detailed analysis of immunological properties of pSC-derived cardiomyocytes and engineered heart muscle (EHM) thereof is, however, lacking. The aim of this study was to determine baseline and cytokine-inducible MHC class I and MHC class II as well as programmed death ligand-1 (PDL-1) and co-stimulatory protein (CD40, CD80, CD86) expression in pSC-derived cardiomyocytes and pSC-EHM in vitro and in vivo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28855356/phase-i-study-of-a-poxviral-tricom-based-vaccine-directed-against-the-transcription-factor-brachyury
#12
Christopher R Heery, Claudia Palena, Sheri McMahon, Renee N Donahue, Lauren M Lepone, Italia Grenga, Ulrike Dirmeier, Lisa Cordes, Jennifer L Marte, William Dahut, Harpreet Singh, Ravi A Madan, Romaine I Fernando, Duane H Hamilton, Jeffrey Schlom, James L Gulley
PURPOSE: The transcription factor brachyury has been shown in preclinical studies to be a driver of the epithelial-to-mesenchymal transition (EMT) and resistance to therapy of human tumor cells. This study describes the characterization of a Modified Vaccinia Ankara (MVA) vector-based vaccine expressing the transgenes for brachyury and three human costimulatory molecules (B7.1, ICAM-1, and LFA-3, designated TRICOM) and a phase I study with this vaccine. EXPERIMENTAL DESIGN: Human dendritic cells (DCs) were infected with MVA-brachyury-TRICOM to define their ability to activate brachyury-specific T cells...
August 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28855348/timing-of-pd-1-blockade-is-critical-to-effective-combination-immunotherapy-with-anti-ox40
#13
David J Messenheimer, Shawn M Jensen, Michael E Afentoulis, Keith W Wegmann, Zipei Feng, David J Friedman, Michael J Gough, Walter J Urba, Bernard A Fox
Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1...
August 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28827658/a-canine-chimeric-monoclonal-antibody-targeting-pd-l1-and-its-clinical-efficacy-in-canine-oral-malignant-melanoma-or-undifferentiated-sarcoma
#14
Naoya Maekawa, Satoru Konnai, Satoshi Takagi, Yumiko Kagawa, Tomohiro Okagawa, Asami Nishimori, Ryoyo Ikebuchi, Yusuke Izumi, Tatsuya Deguchi, Chie Nakajima, Yukinari Kato, Keiichi Yamamoto, Hidetoshi Uemura, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821531/cd28-and-41bb-costimulation-enhances-the-effector-function-of-cd19-specific-engager-t-cells
#15
Mireya Paulina Velasquez, Arpad Szoor, Abishek Vaidya, Aarohi Thakkar, Phuong Nguyen, Meng-Fen Wu, Hao Liu, Stephen Gottschalk
T cells expressing CD19-specific chimeric antigen receptors (CARs) with endodomains that encode a signaling domain derived from CD3zeta and CD28 or 41BB have potent antitumor activity in early phase clinical studies for B-cell malignancies. Besides CD19-specific CARs, other approaches are actively being pursued to redirect T cells to CD19, including recombinant bispecific T-cell engager (BiTE) proteins or T cells genetically modified to express BiTEs (engager [ENG] T cells). Since BiTEs provide no costimulation, we investigated here if provision of costimulation through CD28 and 41BB enhances the effector function of CD19-ENG T cells...
August 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28818684/t-cell-mediated-rejection-of-human-cd34-cells-is-prevented-by-costimulatory-blockade-in-a-xenograft-model
#16
Annie L Oh, Dolores Mahmud, Benedetta Nicolini, Nadim Mahmud, Vitalyi Senyuk, Pritesh R Patel, Elisa Bonetti, Mario Arpinati, James L M Ferrara, Damiano Rondelli
A xenograft model of stem cell rejection was developed by co-transplantating human CD34(+) and allogeneic CD3(+) T cells into NOD-scid ɣ-chain(null) mice. T cells caused graft failure when transplanted at any CD34/CD3 ratio between 1:50 and 1:.1. Kinetics experiments showed that 2 weeks after transplantation CD34(+) cells engrafted the marrow and T cells expanded in the spleen. Then, at 4 weeks only memory T cells populated both sites and rejected CD34(+) cells. Blockade of T cell costimulation was tested by injecting the mice with abatacept (CTLA4-IgG1) from day -1 to +27 (group A), from day -1 to +13 (group B), or from day +14 to +28 (group C)...
August 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28810516/lectin-from-inflorescences-of-ornamental-crop-alpinia-purpurata-acts-on-immune-cells-to-promote-th1-and-th17-responses-nitric-oxide-release-and-lymphocyte-activation
#17
Jéssica de Santana Brito, Gustavo Ramos Salles Ferreira, Emeline Klimczak, Liliya Gryshuk, Nataly Diniz de Lima Santos, Leydianne Leite de Siqueira Patriota, Leyllane Rafael Moreira, Ana Karine Araújo Soares, Bruno Rafael Barboza, Patrícia Maria Guedes Paiva, Daniela Maria do Amaral Ferraz Navarro, Virgínia Maria Barros de Lorena, Cristiane Moutinho Lagos de Melo, Marília Cavalcanti Coriolano, Thiago Henrique Napoleão
Alpinia purpurata is an ornamental crop known as a source of bioactive molecules. This is the first study to report isolation of a lectin (carbohydrate-binding protein) from A. purpurata inflorescences (ApuL). The immunomodulatory potential of ApuL was evaluated by investigating its effects on the production of cytokines and release of nitric oxide by human peripheral blood mononuclear cells (PBMCs). In addition, the differentiation and activation of lymphocytes treated with ApuL was evaluated by immunophenotyping assays...
August 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28807568/function-of-novel-anti-cd19-chimeric-antigen-receptors-with-human-variable-regions-is-affected-by-hinge-and-transmembrane-domains
#18
Leah Alabanza, Melissa Pegues, Claudia Geldres, Victoria Shi, Jed J W Wiltzius, Stuart A Sievers, Shicheng Yang, James N Kochenderfer
Anti-CD19 chimeric antigen receptor (CAR) T cells have caused remissions of B cell malignancies, but problems including cytokine-mediated toxicity and short persistence of CAR T cells in vivo might limit the effectiveness of anti-CD19 CAR T cells. Anti-CD19 CARs that have been tested clinically had single-chain variable fragments (scFvs) derived from murine antibodies. We have designed and constructed novel anti-CD19 CARs containing a scFv with fully human variable regions. T cells expressing these CARs specifically recognized CD19(+) target cells and carried out functions including degranulation, cytokine release, and proliferation...
July 27, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#19
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28791025/the-ido-ahr-axis-controls-th17-treg-immunity-in-a-pulmonary-model-of-fungal-infection
#20
Eliseu Frank de Araújo, Claudia Feriotti, Nayane Alves de Lima Galdino, Nycolas Willian Preite, Vera Lúcia Garcia Calich, Flávio Vieira Loures
In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs)...
2017: Frontiers in Immunology
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