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https://www.readbyqxmd.com/read/29786112/ctla%C3%A2-4-interferes-with-the-hbv%C3%A2-specific-t-cell-immune-response-review
#1
Hui Cao, Ruiwen Zhang, Wei Zhang
Hepatitis B virus (HBV) infection is a major cause of hepatic inflammation. Successful HBV clearance in patients is associated with sustained viral control by effector T cells. Compared with acute hepatitis B, chronic HBV infection is associated with the depletion of T cells, resulting in weak or absent virus‑specific T cells reactivity, which is described as 'exhaustion'. This exhaustion is characterized by impaired cytokine production and sustained expression of multiple coinhibitory molecules. Cytotoxic T lymphocyte‑associated antigen‑4 (CTLA‑4) is one of many coinhibitory molecules that can attenuate T cell activation by inhibiting costimulation and transmitting inhibitory signals to T cells...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29783736/revisiting-cd28-superagonist-tgn1412-as-potential-therapeutic-for-pediatric-b-cell-leukemia-a-review
#2
REVIEW
Katelyn E Brown
Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg ) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell...
May 19, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29767012/corrigendum-to-the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#3
Kannan P Samy, James R Butler, Ping Li, David K C Cooper, Burcin Ekser
[This corrects the article DOI: 10.1155/2017/8415205.].
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29752315/formation-of-immune-complexes-with-a-tetanus-derived-b-cell-epitope-boosts-human-t-cell-responses-to-covalently-linked-peptides-in-an-ex-vivo-blood-loop-system
#4
Erika A K Fletcher, Wendy van Maren, Robert Cordfunke, Jasper Dinkelaar, Jeroen D C Codee, Gijs van der Marel, Cornelis J M Melief, Ferry Ossendorp, Jan Wouter Drijfhout, Sara M Mangsbo
Enhancing T cell responses against both viral and tumor Ags requires efficient costimulation and directed delivery of peptide Ags into APCs. Long peptide vaccines are considered favorable vaccine moieties from a clinical perspective, as they can harbor more than one immunogenic epitope enabling treatment of a broader target population. In addition, longer peptides are not extracellularly loaded on MHC class I; rather, they require intracellular processing and will thereby be presented to T cells mainly by professional APCs, thereby avoiding the risk of tolerance induction...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29751069/extrafoveally-applied-flashing-light-affects-contrast-thresholds-of-achromatic-and-s-cone-isolating-but-not-l-m-cone-modulated-stimuli
#5
A Őze, A Puszta, P Buzás, P Kóbor, G Braunitzer, A Nagy
Flashing light stimulation is often used to investigate the visual system. However, the magnitude of the effect of this stimulus on the various subcortical pathways is not well investigated. The signals of conscious vision are conveyed by the magnocellular, parvocellular and koniocellular pathways. Parvocellular and koniocellular pathways (or more precisely, the L-M opponent and S-cone isolating channels) can be accessed by isoluminant red-green (L-M) and S-cone isolating stimuli, respectively. The main goal of the present study was to explore how costimulation with strong white extrafoveal light flashes alters the perception of stimuli specific to these pathways...
May 8, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29749649/transgelin-2-in-immunity-its-implication-in-cell-therapy
#6
REVIEW
Suin Jo, Hye-Ran Kim, YeVin Mun, Chang-Duk Jun
Transgelin-2 is a small 22-kDa actin-binding protein implicated in actin dynamics, which stabilizes actin structures and participates in actin-associated signaling pathways. Much curiosity regarding transgelin-2 has centered around its dysregulation in tumor development and associated diseases. However, recent studies have shed new light on the functions of transgelin-2, the only transgelin family member present in leukocytes, in the context of various immune responses. In this review, we outlined the biochemical properties of transgelin-2 and its physiological functions in T cells, B cells, and macrophages...
May 11, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29740438/the-nkg2d-nkg2dl-axis-in-the-crosstalk-between-lymphoid-and-myeloid-cells-in-health-and-disease
#7
REVIEW
Ana Stojanovic, Margareta P Correia, Adelheid Cerwenka
Natural killer group 2, member D (NKG2D) receptor is a type II transmembrane protein expressed by both innate and adaptive immune cells, including natural killer (NK) cells, CD8+ T cells, invariant NKT cells, γδ T cells, and some CD4+ T cells under certain pathological conditions. NKG2D is an activating NK receptor that induces cytotoxicity and production of cytokines by effector cells and supports their proliferation and survival upon engagement with its ligands. In both innate and T cell populations, NKG2D can costimulate responses induced by other receptors, such as TCR in T cells or NKp46 in NK cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29737909/abatacept-in-the-treatment-of-psoriatic-arthritis-biological-and-clinical-profiles-of-the-responders
#8
Gaetano Zizzo, Elisa Gremese, Gianfranco Ferraccioli
Abatacept (CTLA4Ig), a selective T-cell costimulation modulator, has been approved for the treatment of psoriatic arthritis patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs, but not for those with uncontrolled skin lesions, nor with axial involvement. In this review, we will try to interpret such a differential efficacy of abatacept on the psoriatic arthritis clinical domains, on the basis of its differential effectiveness on the diverse T-cell subsets at different sites...
May 8, 2018: Immunotherapy
https://www.readbyqxmd.com/read/29731839/high-frequency-of-circulating-follicular-helper-t-cells-is-correlated-with-b-cell-subtypes-in-patients-with-ankylosing-spondylitis
#9
Siqi Long, Li Ma, Dongsheng Wang, Xianwen Shang
T follicular helper (Tfh) cells are known to support effector B cells and enhance autoimmunity; however, the association between the Tfh cells and B cells in ankylosing spondylitis (AS) is unclear. The aim of the present study was to measure the frequency of circulating cluster of differentiation (CD)4+ C-X-C chemokine receptor type 5 (CXCR5)+ Tfh cells and B cell subtypes in peripheral blood from patients with AS, and evaluate the correlation of these factors. Percentages of peripheral blood circulating CD4+ CXCR5+ Tfh cells and B cell subtypes were measured via flow cytometry and the disease activity of individual patients was measured using the Bath AS Disease Activity Index (BASDAI)...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29731774/b7-h1-expression-is-required-for-human-endometrial-regenerative-cells-in-the-prevention-of-transplant-vasculopathy-in-mice
#10
Kui Ye, Xu Lan, Grace Wang, Baoren Zhang, Xiaoxi Xu, Xiang Li, Yiming Zhao, Hao Wang
Vasculopathy is one of the primary pathological changes in chronic rejection of vascularized allograft transplantation. Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells with immunosuppressive effect. B7-H1 is a negative costimulator that mediates active immune suppression. The aim of this study was to investigate the requirement of B7-H1 in the immunoregulation of ERCs in preventing transplant vasculopathy of aorta allografts. The results showed that B7-H1 expression on ERCs was upregulated by IFN- γ in a dose-dependent manner and it was required for ERCs to inhibit the proliferation of peripheral blood mononuclear cells (PBMCs) in vitro ...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29723921/de-novo-belatacept-in-clinical-vascularized-composite-allotransplantation
#11
Linda C Cendales, David S Ruch, Adela R Cardones, Guy Potter, Joshua Dooley J, Daniel Dore, Jonah Orr, Gregory Ruskin, Minqing Song, Dong-Feng Chen, Maria A Selim, Allan D Kirk
Most immunosuppressive regimens used in clinical vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)-based. As such, most recipients have experienced CNI-related side effects. Costimulation blockade, specifically CD28/B7 inhibition with belatacept, has emerged as a clinical replacement for CNI-based immunosuppression in kidney transplantation. We have previously shown that belatacept can be used as a centerpiece immunosuppressant for VCA in non-human primates, and subsequently reported successful conversion from a CNI-based regimen to a belatacept-based regimen after clinical hand transplantation...
May 3, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29701246/early-programming-and-late-acting-checkpoints-governing-the-development-of-cd4-t-cell-memory
#12
REVIEW
Kunal Dhume, K Kai McKinstry
CD4 T cells contribute to protection against pathogens through numerous mechanisms. Incorporating the goal of memory CD4 T cell generation into vaccine strategies thus offers a powerful approach to improve their efficacy, especially in situations where humoral responses alone cannot confer long-term immunity. These threats include viruses such as influenza that mutate coat proteins to avoid neutralizing antibodies, but that are targeted by T cells that recognize more conserved protein epitopes shared by different strains...
April 27, 2018: Immunology
https://www.readbyqxmd.com/read/29697355/genetic-variation-of-costimulatory-molecules-including-cytotoxic-t-lymphocyte-antigen-4-inducible-t-cell-costimulator-cluster-differentiation-28-and-programmed-cell-death-1-genes-in-iranian-patients-with-leukemia
#13
Mani Ramzi, Nargess Arandi, Mahdiyar Iravani Saadi, Ramin Yaghobi, Bita Geramizadeh
OBJECTIVES: There are limited studies about the possible relationship between genetic variations of costimulatory genes and susceptibility to hematologic malignancies like leukemia and lymphoma. MATERIALS AND METHODS: This cross-sectional study included 59 leukemia patients. The polymorphisms of costimulatory molecules, including the CTLA-4 gene (-318 C/T, -1722 T/C, -1661 A/G, +49 A/G), PD-1 gene (1.3 A/G, 1.9 C/T), ICOS gene (1720 C/T), and CD28 gene (17 C/T), were analyzed by polymerase chain reaction-restriction fragment length polymorphism methods...
April 26, 2018: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/29691324/suppression-of-costimulation-by-human-cytomegalovirus-promotes-evasion-of-cellular-immune-defenses
#14
Eddie C Y Wang, Mariana Pjechova, Katie Nightingale, Virginia-Maria Vlahava, Mihil Patel, Eva Ruckova, Simone K Forbes, Luis Nobre, Robin Antrobus, Dawn Roberts, Ceri A Fielding, Sepehr Seirafian, James Davies, Isa Murrell, Betty Lau, Gavin S Wilkie, Nicolás M Suárez, Richard J Stanton, Borivoj Vojtesek, Andrew Davison, Paul J Lehner, Michael P Weekes, Gavin W G Wilkinson, Peter Tomasec
CD58 is an adhesion molecule that is known to play a critical role in costimulation of effector cells and is intrinsic to immune synapse structure. Herein, we describe a virally encoded gene that inhibits CD58 surface expression. Human cytomegalovirus (HCMV) UL148 was necessary and sufficient to promote intracellular retention of CD58 during HCMV infection. Blocking studies with antagonistic anti-CD58 mAb and an HCMV UL148 deletion mutant (HCMV∆UL148) with restored CD58 expression demonstrated that the CD2/CD58 axis was essential for the recognition of HCMV-infected targets by CD8+ HCMV-specific cytotoxic T lymphocytes (CTLs)...
April 24, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29678951/cyclooxygenase-1-and-2-play-contrasting-roles-in-listeria-stimulated-immunity
#15
Erin Theisen, Courtney E McDougal, Masako Nakanishi, David M Stevenson, Daniel Amador-Noguez, Daniel W Rosenberg, Laura J Knoll, John-Demian Sauer
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity and are commonly used for pain relief and fever reduction. NSAIDs are used following childhood vaccinations and cancer immunotherapies; however, how NSAIDs influence the development of immunity following these therapies is unknown. We hypothesized that NSAIDs would modulate the development of an immune response to Listeria monocytogenes -based immunotherapy. Treatment of mice with the nonspecific COX inhibitor indomethacin impaired the generation of cell-mediated immunity...
April 20, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29678874/mitochondrial-morphological-and-functional-reprogramming-following-cd137-4-1bb-co-stimulation
#16
Alvaro Teijeira, Sara Labiano, Saray Garasa, Inaki Etxeberria, Eva Santamaria, Ana Rouzaut, Michel Enamorado, Arantza Azpilikueta, Susana Inoges, Elixabet Bolanos-Mateo, Maria Angela Aznar, Alfonso R Sanchez-Paulete, David Sancho, Ignacio Melero
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression...
April 20, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29676593/icos-costimulation-differentially-affects-t-cells-in-secondary-lymphoid-organs-and-inflamed-tissues
#17
Dana Vu Van, Laura Bauer, Richard A Kroczek, Andreas Hutloff
B cell interaction with follicular helper T cells and their subsequent differentiation into high-affinity antibody producing cells normally takes place in secondary lymphoid organs. The costimulator ICOS plays a key role in this process and is therefore considered as an attractive target to modulate exaggerated B cell responses in autoimmune or allergic diseases. Inflamed tissues were recently recognized as additional sites of active T cell/B cell interaction. To analyze whether ICOS costimulation is also important there, we employed a mouse airway inflammation model which allows to directly compare immune reactions in the lung-draining lymph node and the lung tissue and also to assess the relative importance of dendritic cells versus B cells as antigen-presenting cells...
April 20, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29674640/the-cpt1a-inhibitor-etomoxir-induces-severe-oxidative-stress-at-commonly-used-concentrations
#18
Roddy S O'Connor, Lili Guo, Saba Ghassemi, Nathaniel W Snyder, Andrew J Worth, Liwei Weng, Yoonseok Kam, Benjamin Philipson, Sophie Trefely, Selene Nunez-Cruz, Ian A Blair, Carl H June, Michael C Milone
Etomoxir (ETO) is a widely used small-molecule inhibitor of fatty acid oxidation (FAO) through its irreversible inhibitory effects on the carnitine palmitoyl-transferase 1a (CPT1a). We used this compound to evaluate the role of fatty acid oxidation in rapidly proliferating T cells following costimulation through the CD28 receptor. We show that ETO has a moderate effect on T cell proliferation with no observable effect on memory differentiation, but a marked effect on oxidative metabolism. We show that this oxidative metabolism is primarily dependent upon glutamine rather than FAO...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29670037/expression-and-regulation-of-thymic-stromal-lymphopoietin-and-thymic-stromal-lymphopoietin-receptor-heterocomplex-in-the-innate-adaptive-immunity-of-pediatric-asthma
#19
REVIEW
Sheng-Chieh Lin, Fang-Yi Cheng, Jun-Jen Liu, Yi-Ling Ye
Asthma is a chronic inflammatory disease affecting the airway, and it is characterized by a wheezing breathing sound, variable airflow obstruction and the presence of inflammatory cells in the submucosa of the bronchi. Viral infection, pollutants and sensitivity to aeroallergens damage the epithelium from childhood, which causes asthma. The pathogenesis of asthma includes pathways of innate stimulation by environmental microbes and irritant pathogens. Damaged epithelial cells produce thymic stromal lymphopoietin (TSLP) and stimulate myeloid dendritic cell maturation through the thymic stromal lymphopoietin receptor (TSLPR) heterocomplex...
April 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29657830/conversion-to-seronegative-status-after-abatacept-treatment-in-patients-with-early-and-poor-prognostic-rheumatoid-arthritis-is-associated-with-better-radiographic-outcomes-and-sustained-remission-post-hoc-analysis-of-the-agree-study
#20
Diahann T S L Jansen, Paul Emery, Josef S Smolen, Rene Westhovens, Manuela Le Bars, Sean E Connolly, June Ye, René E M Toes, Tom W J Huizinga
Objective: To evaluate the effects of the T-cell costimulation blocker abatacept on anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in early rheumatoid arthritis (RA), and associations between changes in serological status and clinical response. Methods: Post hoc analysis of the phase III AGREE study in methotrexate (MTX)-naïve patients with early RA and poor prognostic factors. Patients were randomised to abatacept (~10 mg/kg intravenously according to weight range) or placebo, plus MTX over 12 months followed by open-label abatacept plus MTX for 12 months...
2018: RMD Open
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