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https://www.readbyqxmd.com/read/27908931/filling-the-tank-keeping-antitumor-t-cells-metabolically-fit-for-the-long-haul
#1
REVIEW
Greg M Delgoffe
Discoveries in tumor immunology and subsequent clinical advances in cancer immunotherapy have revealed that the immune system is not oblivious to tumor progression but heavily interacts with developing neoplasia and malignancy. A major factor preventing immune destruction is the establishment of a highly immunosuppressive tumor microenvironment (TME), which provides architecture to the tumor, supports indirect means of immunosuppression such as the recruitment of tolerogenic cells like regulatory T cells and myeloid-derived suppressor cells (MDSC), and represents a zone of metabolically dearth conditions...
December 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27904945/-sarcoidosis-and-uveitis-an-update
#2
REVIEW
J G Garweg
Ocular involvement in sarcoidosis is present in up to one third of patients and is frequently manifested before the underlying systemic disease has been diagnosed. With a view to the therapeutic consequences an early diagnosis of the underlying disease is advantageous. In cases of visual loss early diagnostic measures include invasive procedures, such as ultrasound-guided bronchoalveolar lavage and transbronchial biopsy, if nodular conjunctival or cutaneous manifestations which would confirm the diagnosis are not present...
November 30, 2016: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/27890932/il-10-production-by-cll-cells-is-enhanced-in-the-anergic-ighv-mutated-subset-and-associates-with-reduced-dna-methylation-of-the-il10-locus
#3
S Drennan, A D'Avola, Y Gao, C Weigel, E Chrysostomou, A J Steele, T Zenz, C Plass, P W Johnson, A P Williams, G Packham, F K Stevenson, C C Oakes, F Forconi
Chronic lymphocytic leukemias (CLL) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce IL-10. The two subsets differ in their levels of anergy, defined by low surface IgM levels/signaling capacity, and in their DNA methylation profile, particularly variable in M-CLL. We have now found that levels of IL-10 produced by activated CLL cells were highly variable. Levels were higher in M-CLL than in U-CLL and correlated with anergy...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27830696/igd-attenuates-the-igm-induced-anergy-response-in-transitional-and-mature-b-cells
#4
Zahra Sabouri, Samuel Perotti, Emily Spierings, Peter Humburg, Mehmet Yabas, Hannes Bergmann, Keisuke Horikawa, Carla Roots, Samantha Lambe, Clara Young, T Dan Andrews, Matthew Field, Anselm Enders, Joanne H Reed, Christopher C Goodnow
Self-tolerance by clonal anergy of B cells is marked by an increase in IgD and decrease in IgM antigen receptor surface expression, yet the function of IgD on anergic cells is obscure. Here we define the RNA landscape of the in vivo anergy response, comprising 220 induced sequences including a core set of 97. Failure to co-express IgD with IgM decreases overall expression of receptors for self-antigen, but paradoxically increases the core anergy response, exemplified by increased Sdc1 encoding the cell surface marker syndecan-1...
November 10, 2016: Nature Communications
https://www.readbyqxmd.com/read/27776110/e3-ubiquitin-ligase-rnf128-promotes-innate-antiviral-immunity-through-k63-linked-ubiquitination-of-tbk1
#5
Guanhua Song, Bingyu Liu, Zhihui Li, Haifeng Wu, Peng Wang, Kai Zhao, Guosheng Jiang, Lei Zhang, Chengjiang Gao
TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo...
December 2016: Nature Immunology
https://www.readbyqxmd.com/read/27759162/increased-endogenous-antigen-presentation-in-the-periphery-enhances-susceptibility-to-inflammation-induced-gastric-autoimmunity-in-mice
#6
Sarah A Overall, Dorothée Bourges, Ian R van Driel, Paul A Gleeson
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H(+) /K(+) ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice...
October 19, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27697466/diacylglycerol-kinases-in-cancer
#7
Isabel Mérida, Pedro Torres-Ayuso, Antonia Ávila-Flores, Javier Arranz-Nicolás, Elena Andrada, María Tello-Lafoz, Rosa Liébana, Raquel Arcos
Diacylglycerol kinases (DGK) are a family of enzymes that catalyze the transformation of diacylglycerol into phosphatidic acid. In T lymphocytes, DGKα and ζ limit the activation of the PLCγ/Ras/ERK axis, providing a critical checkpoint to inhibit T cell responses. Upregulation of these isoforms limits Ras activation, leading to hypo-responsive, anergic states similar to those caused by tumors. Recent studies have identified DGKα upregulation in tumor lymphocyte infiltrates, and cells from DGKα and ζ deficient mice show enhanced antitumor activity, suggesting that limitation of DAG based signals by DGK is used by tumors to evade immune attack...
September 23, 2016: Advances in Biological Regulation
https://www.readbyqxmd.com/read/27676155/coexistence-of-th1-th2-and-th17-treg-imbalances-in-patients-with-post-traumatic-sepsis
#8
Dublu Lal Gupta, Sanjeev Bhoi, Teena Mohan, Sagar Galwnkar, D N Rao
INTRODUCTION: Multiple organ dysfunction syndrome (MODS) developed due to the insult of trauma is a leading cause of death. The high mortality rate in these patients with and without sepsis has been reported up to 50%, throughout the world and thus required an urgent insight to overcome this problem. OBJECTIVE: The aim of this study is to examine the differential changes in subsets of T cells, imbalance in cytokine profile, immune-paralysis (T cell anergy) in Trauma hemorrhagic shock (THS) and post traumatic sepsis patients...
December 2016: Cytokine
https://www.readbyqxmd.com/read/27622045/a-novel-tlr7-agonist-reverses-nk-cell-anergy-and-cures-rma-s-lymphoma-bearing-mice
#9
Gabriela Maria Wiedemann, Severin Johannes Jacobi, Michael Chaloupka, Angelina Krächan, Svetlana Hamm, Stefan Strobl, Roland Baumgartner, Simon Rothenfusser, Peter Duewell, Stefan Endres, Sebastian Kobold
Toll-like receptor 7 (TLR7) agonists are potent immune stimulants able to overcome cancer-associated immune suppression. Due to dose-limiting systemic toxicities, only the topically applied TLR7 agonist (imiquimod) has been approved for therapy of skin tumors. There is a need for TLR7-activating compounds with equivalent efficacy but less toxicity. SC1, a novel small molecule agonist for TLR7, is a potent type-1 interferon inducer, comparable to the reference TLR7 agonist resiquimod, yet with lower induction of proinflammatory cytokines...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27591335/costimulation-blockade-in-autoimmunity-and-transplantation-the-cd28-pathway
#10
Andrew B Adams, Mandy L Ford, Christian P Larsen
T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. TCR signaling in the absence of costimulatory signals can lead to an abortive attempt at activation and subsequent anergy. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. The development of the fusion protein CTLA-4-Ig as an experimental and subsequent therapeutic tool is one of the major success stories in modern immunology...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27562586/in-vivo-gene-delivery-to-lymph-node-stromal-cells-leads-to-transgene-specific-cd8-t-cell-anergy-in-mice
#11
Séverine Ciré, Sylvie Da Rocha, Maxime Ferrand, Mary K Collins, Anne Galy
Lymph node stromal cells play a role in self-tolerance by presenting tissue antigens to T cells. Yet, immunomodulatory properties of lymphoid tissue stroma, particularly toward CD4+ T cells, remain insufficiently characterized by lack of tools to target antigens for presentation by stromal cells. A lentiviral vector was therefore designed for antigen delivery to MHC class II(+) cells of nonhematopoietic origin. Following intravenous vector delivery, the transgene was detected in lymph node gp38+ stromal cells which were CD45- MHCII+ and partly positive for CD86 and CTLA4 or B7-H4...
October 4, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27552242/the-first-case-report-of-anaphylaxis-caused-by-the-inclusion-complex-of-rocuronium-and-sugammadex
#12
Grace Ho, Russell C Clarke, Paul H M Sadleir, Peter R Platt
A 50-year-old man developed a severe anaphylactic reaction shortly after the administration of sugammadex at the end of an uneventful laparoscopic appendectomy. Subsequent skin testing was negative to all agents to which the patient was exposed including sugammadex. Because of the temporal relationship to the administration of sugammadex, further skin testing was performed with premixed sugammadex and rocuronium that produced a markedly positive response. This is the first case report of anergy to the individual components but sensitivity to the inclusion complex of rocuronium and sugammadex...
August 22, 2016: A & A Case Reports
https://www.readbyqxmd.com/read/27543653/cell-cycle-arrest-caused-by-mek-erk-signaling-is-a-mechanism-for-suppressing-growth-of-antigen-hyperstimulated-effector-t-cells
#13
Shizuka Ohtsuka, Shuhei Ogawa, Ei Wakamatsu, Ryo Abe
Suppression of T-cell growth is an important mechanism for establishment of self-tolerance and prevention of unwanted prolonged immune responses that may cause tissue damage. Although negative selection of potentially self-reactive T cells in the thymus as well as in peripheral tissues has been extensively investigated and well documented, regulatory mechanisms to dampen proliferation of antigen-specific effector T cells in response to antigen stimulation remain largely unknown. Thus, in this work, we focus on the identification of growth suppression mechanisms of antigen-specific effector T cells...
November 2016: International Immunology
https://www.readbyqxmd.com/read/27526967/liver-immunology-how-to-reconcile-tolerance-with-autoimmunity
#14
Charlotte R Grant, Rodrigo Liberal
There are several examples of liver tolerance: the relative ease by which liver allografts are accepted and the exploitation of the hepatic microenvironment by the malarial parasite and hepatotrophic viruses are notable examples. The vasculature of the liver supports a unique population of antigen presenting cells specialised to maintain immunological tolerance despite continuous exposure to gut-derived antigens. Liver sinusoidal endothelial cells and Kupffer cells appear to be key to the maintenance of immune tolerance, by promoting T cell anergy or deletion and the generation of regulatory cell subsets...
August 12, 2016: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/27525406/-viral-superantigens
#15
Dürdal Us
Superantigens (SAgs) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of T cells via an unconventional mechanism. They cause polyclonal activation of T cells in a non-specific manner, by binding to a particular variable-beta (Vβ) chain of T-cell receptor (TCR) and MHC class II molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the T cell. SAgs are classified into three groups, namely 1) exogenous (soluble proteins and exotoxins secreted by microorganisms), 2) endogenous (transmembrane proteins encoded by viruses which are integrated into the genome) and 3) B-cell SAgs (proteins which stimulate predominantly B cells)...
July 2016: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/27485011/tolerogenic-dendritic-cells-for-reprogramming-of-lymphocyte-responses-in-autoimmune-diseases
#16
Paulina García-González, Gabriela Ubilla-Olguín, Diego Catalán, Katina Schinnerling, Juan Carlos Aguillón
Dendritic cells (DCs) control immune responses by driving potent inflammatory actions against external and internal threats while generating tolerance to self and harmless components. This duality and their potential to reprogram immune responses in an antigen-specific fashion have made them an interesting target for immunotherapeutic strategies to control autoimmune diseases. Several protocols have been described for in vitro generation of tolerogenic DCs (tolDCs) capable of modulating adaptive immune responses and restoring tolerance through different mechanisms that involve anergy, generation of regulatory lymphocyte populations, or deletion of potentially harmful inflammatory T cell subsets...
July 30, 2016: Autoimmunity Reviews
https://www.readbyqxmd.com/read/27476883/tweaking-mesenchymal-stem-progenitor-cell-immunomodulatory-properties-with-viral-vectors-delivering-cytokines
#17
Paola Quaranta, Daniele Focosi, Giulia Freer, Mauro Pistello
Mesenchymal Stem Cells (MSCs) can be found in various body sites. Their main role is to differentiate into cartilage, bone, muscle, and fat cells to allow tissue maintenance and repair. During inflammation, MSCs exhibit important immunomodulatory properties that are not constitutive, but require activation, upon which they may exert immunosuppressive functions. MSCs are defined as "sensors of inflammation" since they modulate their ability of interfering with the immune system both in vitro and in vivo upon interaction with different factors...
September 15, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27459422/combinatorial-immunotherapeutic-approaches-to-restore-the-function-of-anergic-tumor-reactive-cytotoxic-cd8-t-cells
#18
William L Redmond, Stefanie N Linch
Numerous preclinical studies have demonstrated that combination immunotherapy can significantly reduce tumor growth and improve overall survival as compared to monotherapy. Furthermore, dual CTLA-4/PD-1 checkpoint blockade recently received FDA-approval for patients with metastatic melanoma, becoming the first combination immunotherapy to garner this designation in a rapidly evolving field. Despite this progress, the majority of patients do not respond to treatment, underscoring the critical need for more effective therapies...
July 26, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27448585/immediate-dysfunction-of-vaccine-elicited-cd8-t-cells-primed-in-the-absence-of-cd4-t-cells
#19
Nicholas M Provine, Rafael A Larocca, Malika Aid, Pablo Penaloza-MacMaster, Alexander Badamchi-Zadeh, Erica N Borducchi, Kathleen B Yates, Peter Abbink, Marinela Kirilova, David Ng'ang'a, Jonathan Bramson, W Nicholas Haining, Dan H Barouch
CD4(+) T cell help is critical for optimal CD8(+) T cell memory differentiation and maintenance in many experimental systems. In addition, many reports have identified reduced primary CD8(+) T cell responses in the absence of CD4(+) T cell help, which often coincides with reduced Ag or pathogen clearance. In this study, we demonstrate that absence of CD4(+) T cells at the time of adenovirus vector immunization of mice led to immediate impairments in early CD8(+) T cell functionality and differentiation. Unhelped CD8(+) T cells exhibited a reduced effector phenotype, decreased ex vivo cytotoxicity, and decreased capacity to produce cytokines...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27435215/ceacam1-mediates-b-cell-aggregation-in-central-nervous-system-autoimmunity
#20
Damiano M Rovituso, Laura Scheffler, Marie Wunsch, Christoph Kleinschnitz, Sebastian Dörck, Jochen Ulzheimer, Antonios Bayas, Lawrence Steinman, Süleyman Ergün, Stefanie Kuerten
B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1(+) B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84...
July 20, 2016: Scientific Reports
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