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T cell signaling

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https://www.readbyqxmd.com/read/27933753/mass-cytometry-of-follicular-lymphoma-tumors-reveals-intrinsic-heterogeneity-in-proteins-including-hla-dr-and-a-deficit-in-non-malignant-plasmablast-and-germinal-center-b-cell-populations
#1
Cara Ellen Wogsland, Allison Rae Greenplate, Arne Kolstad, June Helen Myklebust, Jonathan Michael Irish, Kanutte Huse
BACKGROUND: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the non-malignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity. METHODS: Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, non-malignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933701/ccr2-mediates-helicobacter-pylori-induced-immune-tolerance-and-contributes-to-mucosal-homeostasis
#2
Xia Sun, Min Zhang, Mohamad El-Zaatari, Gray B Huffnagle, John Y Kao
BACKGROUND: We previously demonstrated that H. pylori infection leads to increased induction of regulatory T cells in local and systemic immune compartments. Here, we investigate the role of CCR2 in the tolerogenic programing of dendritic cells in a mouse model of H. pylori infection. MATERIALS AND METHODS: CCR2 deficient (CCR2KO) mice and wild-type (Wt) mice infected with H. pylori SS1 strain were analyzed by qPCR and FACS analysis. In vitro, bone marrow-derived DC on day 6 from CCR2KO and Wt mice cocultured with or without H...
December 8, 2016: Helicobacter
https://www.readbyqxmd.com/read/27933672/single-neuron-activity-and-theta-modulation-in-the-posterior-parietal-cortex-in-a-visuospatial-attention-task
#3
Fang-Chi Yang, T K Jacobson, R D Burwell
The posterior parietal cortex (PPC) is implicated in directing and maintaining visual attention to locations in space. We hypothesized that the PPC also engages other cognitive processes in the transformation of behaviorally relevant visual inputs into appropriate actions, for example, monitoring of multiple locations, selection of responses to locations in space, and monitoring the outcome of response selections. We recorded single cells and local field potentials in the rat PPC during performance on a novel visuospatial attention (VSA) task that requires visually monitoring locations in space in order to make appropriate stimulus-guided locomotor responses...
December 9, 2016: Hippocampus
https://www.readbyqxmd.com/read/27933315/immunogenicity-of-self-tumor-associated-proteins-is-enhanced-through-protein-truncation
#4
Tim Kottke, Kevin G Shim, Vanesa Alonso-Camino, Shane Zaidi, Rosa Maria Diaz, Jose Pulido, Jill Thompson, Karishma R Rajani, Laura Evgin, Elizabeth Ilett, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Vile
We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own poly-A signal, viral species emerged in culture which had deleted the cellular poly-A signal and also contained a truncated form of the protein coding sequence. Typically, the truncation occurred such that a Tyrosine-encoding codon was converted into a STOP codon. We believe that the truncation of tumor-associated proteins expressed from VSV in this way occurred to preserve the ability of the virus to replicate efficiently...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933313/genetic-engineering-of-chimeric-antigen-receptors-using-lamprey-derived-variable-lymphocyte-receptors
#5
Robert Moot, Sunil S Raikar, Lauren Fleischer, Melissa Querrey, Daniel E Tylawsky, Hirotomo Nakahara, Christopher B Doering, H Trent Spencer
Chimeric antigen receptors (CARs) are used to redirect effector cell specificity to selected cell surface antigens. Using CARs, antitumor activity can be initiated in patients with no prior tumor specific immunity. Although CARs have shown promising clinical results, the technology remains limited by the availability of specific cognate cell target antigens. To increase the repertoire of targetable tumor cell antigens we utilized the immune system of the sea lamprey to generate directed variable lymphocyte receptors (VLRs)...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933292/nitric-oxide-modulates-postnatal-bone-marrow-derived-mesenchymal-stem-cell-migration
#6
John W Fuseler, Mani T Valarmathi
Nitric oxide (NO) is a small free-radical gas molecule, which is highly diffusible and can activate a wide range of downstream effectors, with rapid and widespread cellular effects. NO is a versatile signaling mediator with a plethora of cellular functions. For example, NO has been shown to regulate actin, the microfilament, dependent cellular functions, and also acts as a putative stem cell differentiation-inducing agent. In this study, using a wound-healing model of cellular migration, we have explored the effect of exogenous NO on the kinetics of movement and morphological changes in postnatal bone marrow-derived mesenchymal stem cells (MSCs)...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27933066/functionally-diverse-nk-like-t-cells-are-effectors-and-predictors-of-successful-aging
#7
REVIEW
Joshua J Michel, Patricia Griffin, Abbe N Vallejo
The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27933060/regulators-of-tfh-cell-differentiation
#8
REVIEW
Gajendra M Jogdand, Suchitra Mohanty, Satish Devadas
The follicular helper T (Tfh) cells help is critical for activation of B cells, antibody class switching, and germinal center (GC) formation. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), ICOS, programed death 1 (PD-1), B cell lymphoma 6 (BCL-6), and IL-21. They are involved in clearing infections and are adversely linked with autoimmune diseases and also have a role in viral replication as well as clearance. On the one hand, Tfh cells are generated from naive CD4(+) T cells with sequential steps involving cytokine signaling (IL-21, IL-6, IL-12, activin A), migration, and positioning in the GC by CXCR5, surface receptors (ICOS/ICOSL, signaling lymphocyte activation molecule-associated protein/signaling lymphocyte activation molecule) as well as transcription factor (BCL-6, c-Maf, and signal transducer and activator of transcription 3) signaling and repressor miR155...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27932994/comparative-mrna-and-microrna-profiling-during-acute-myocardial-infarction-induced-by-coronary-occlusion-and-ablation-radio-frequency-currents
#9
Eduardo T Santana, Regiane Dos Santos Feliciano, Andrey J Serra, Eduardo Brigidio, Ednei L Antonio, Paulo J F Tucci, Lubov Nathanson, Mariana Morris, José A Silva
The ligation of the left anterior descending coronary artery is the most commonly used experimental model to induce myocardial infarction (MI) in rodents. A high mortality in the acute phase and the heterogeneity of the size of the MI obtained are drawbacks recognized in this model. In an attempt to solve the problem, our group recently developed a new MI experimental model which is based on application of myocardial ablation radio-frequency currents (AB-RF) that yielded MI with homogeneous sizes and significantly reduce acute mortality...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27932942/loss-of-fractalkine-signaling-exacerbates-axon-transport-dysfunction-in-a-chronic-model-of-glaucoma
#10
Kevin T Breen, Sarah R Anderson, Michael R Steele, David J Calkins, Alejandra Bosco, Monica L Vetter
Neurodegeneration in glaucoma results in decline and loss of retinal ganglion cells (RGCs), and is associated with activation of myeloid cells such as microglia and macrophages. The chemokine fractalkine (FKN or Cx3cl1) mediates communication from neurons to myeloid cells. Signaling through its receptor Cx3cr1 has been implicated in multiple neurodegenerative diseases, but the effects on neuronal pathology are variable. Since it is unknown how FKN-mediated crosstalk influences RGC degeneration in glaucoma, we assessed this in a chronic mouse model, DBA/2J...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27932698/identification-of-inhibitors-of-the-association-of-zap-70-with-the-t-cell-receptor-by-high-throughput-screen
#11
Patrick R Visperas, Christopher G Wilson, Jonathan A Winger, Qingrong Yan, Kevin Lin, Michelle R Arkin, Arthur Weiss, John Kuriyan
ZAP-70 is a critical molecule in the transduction of T cell antigen receptor signaling and the activation of T cells. Upon activation of the T cell antigen receptor, ZAP-70 is recruited to the intracellular ζ-chains of the T cell receptor, where ZAP-70 is activated and colocalized with its substrates. Inhibitors of ZAP-70 could potentially function as treatments for autoimmune diseases or organ transplantation. In this work, we present the design, optimization, and implementation of a screen for inhibitors that would disrupt the interaction between ZAP-70 and the T cell antigen receptor...
December 8, 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/27932584/the-eif3-complex-of-typanosoma-brucei-composition-conservation-does-not-imply-the-conservation-of-structural-assembly-and-subunits-function
#12
Kunrao Li, Shuru Zhou, Qixuan Guo, Xin Chen, Dehua Lai, Zhaorong Lun, Xuemin Guo
The multisubunit eukaryotic initiation factor 3 (eIF3) plays multiple roles in translation, but poorly understood in trypanosomes. The putative subunits eIF3a and eIF3f of Trypanosoma brucei (TbIF3a and TbIF3f) were overexpressed and purified, and 11 subunits were identified, TbIF3a through l minus j, which form a tight complex. Both TbIF3a and TbIF3f are essential for viability of T. brucei. RNAi knockdown of either of them severely reduced total translation and the ratio of polysome/80S peak area. TbIF3f and TbIF3a RNAi cell lines were modified to express tagged-TbIF3a and -TbIF3f, respectively...
December 8, 2016: RNA
https://www.readbyqxmd.com/read/27932527/mechanisms-of-in-vivo-ribosome-maintenance-change-in-response-to-nutrient-signals
#13
Andrew D Mathis, Bradley C Naylor, Richard H Carson, Eric Evans, Justin Harwell, Jared Knect, Eric Hexem, Fredrick Peelor, Benjamin F Miller, Karyn L Hamilton, Mark K Transtrum, Benjamin T Bikman, John C Price
Control of protein homeostasis is fundamental to the health and longevity of all organisms. Because the rate of protein synthesis by ribosomes is a central control point in this process, regulation and maintenance of ribosome function could have amplified importance in the overall regulatory circuit. Indeed, ribosomal defects are commonly associated with loss of protein homeostasis, aging and disease, whereas improved protein homeostasis, implying optimal ribosomal function, is associated with disease resistance and increased lifespan...
December 8, 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/27931590/cytotoxic-t-lymphocyte-associated-protein-4-acts-on-local-draining-lymph-nodes-in-the-allogeneic-abdominal-skin-flap-of-a-rat-model-to-extend-its-survival
#14
G Ma, J Pei, Y Li, Y Han, D Liu
BACKGROUND: Early acute allograft rejection is the result of immune cells mainly composed of thymocyte (T) cells, which are activated, mature, and differentiate in lymphoid tissue. METHODS: Cytotoxic T lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) competitively suppresses the cluster of differentiation 28/CTLA4-B7 costimulatory signaling pathway and alters the ratio of T helper 1 to T helper 2, leading to the inhibition of T cell activation. RESULTS: We used lentivirus-packed CTLA4-Ig to infect the local draining lymph nodes of the allograft skin flap in a rat model, which effectively extended the survival of the allograft...
December 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931536/advances-in-atopic-dermatitis-in-2015
#15
REVIEW
Takashi Nomura, Kenji Kabashima
This review aims to highlight recently published articles on atopic dermatitis (AD). Updated are the insights into epidemiology, pathology, diagnostics, and therapy. Epidemiologic studies have revealed a positive correlation between AD and systemic conditions, such as rheumatoid arthritis, inflammatory bowel disease, and neonatal adiposity. Pathologic findings highlight the involvement of novel barrier factors (desmoplakin and claudin), novel immune cell subsets (pathogenic effector TH2 cells and group 2 innate lymphoid cells), and differential skewing of helper T cells (eg, TH17 dominance in Asians with AD)...
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27931222/mir-15a-16-reduces-retinal-leukostasis-through-decreased-pro-inflammatory-signaling
#16
Eun-Ah Ye, Li Liu, Youde Jiang, Jenny Jan, Subhash Gaddipati, Susmit Suvas, Jena J Steinle
BACKGROUND: Hyperglycemia is a significant risk factor for diabetic retinopathy and induces increased inflammatory responses and retinal leukostasis, as well as vascular damage. Although there is an increasing amount of evidence that miRNA may be involved in the regulation in the pathology of diabetic retinopathy, the mechanisms by which miRNA mediate cellular responses to control onset and progression of diabetic retinopathy are still unclear. The purpose of our study was to investigate the hypothesis that miR-15a/16 inhibit pro-inflammatory signaling to reduce retinal leukostasis...
December 8, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27931083/the-therapeutic-potential-of-t-cell-metabolism
#17
Ali Zarrinpar, Steven J Bensinger
Transplant rejection mediated by the adaptive immune system remains a major barrier to achieving long-term tolerance and graft survival. Emerging evidence indicates that lymphocytes rapidly shift their metabolic programs in response to activation, co-stimulatory, and cytokine signals to support required effector cell differentiation and function. These observations have led to the hypothesis that manipulating the metabolic programs of immune cells could serve as a powerful therapeutic strategy for attenuating deleterious immune responses and facilitating durable tolerance in the setting of allogeneic solid organ or bone marrow transplant...
December 8, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27931022/hydrogen-sulfide-and-t-type-ca2-channels-in-pain-processing-neuronal-differentiation-and-neuroendocrine-secretion
#18
Kazuki Fukami, Fumiko Sekiguchi, Atsufumi Kawabata
BACKGROUND: Hydrogen sulfide (H2S), a gasotransmitter, is generated from L-cysteine by mainly 3 enzymes, cystathionine-γ-lyase (CSE), cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase in cooperation with cysteine aminotransferase. The H2S-forming enzymes, particularly CSE, are overexpressed under the pathological conditions such as inflammation, neuronal or neuroendocrine differentiation and cancer development. Given that Cav3.2 T-type Ca2+ channels mediate some of the biological activity of H2S, we focus on the role of the H2S/Cav3...
December 9, 2016: Pharmacology
https://www.readbyqxmd.com/read/27930920/indoleamine-2-3-dioxygenase-regulates-t-cell-activity-through-vav1-rac-pathway
#19
Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected...
December 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27930745/the-ebola-interferon-inhibiting-domains-attenuate-and-dysregulate-cell-mediated-immune-responses
#20
Ndongala Michel Lubaki, Patrick Younan, Rodrigo I Santos, Michelle Meyer, Mathieu Iampietro, Richard A Koup, Alexander Bukreyev
Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m)...
December 2016: PLoS Pathogens
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