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Immunological synapse

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https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#1
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28608562/t11ts-immunotherapy-repairs-pi3k-akt-signaling-in-t-cells-clues-towards-enhanced-t-cell-survival-in-rat-glioma-model
#2
Suhnrita Chaudhuri, Manoj Kumar Singh, Debanjan Bhattacharya, Ankur Datta, Iman Hazra, Somnath Mondal, Omar Faruk Sk Md, Larance Ronsard, Tushar Kanti Ghosh, Swapna Chaudhuri
Malignant glioma is the most fatal of astrocytic lineage tumors despite therapeutic advances. Onset and progression of gliomas is accompanied by severe debilitation of T-cell defense and T-cell survival. One of the chief contributors to T-cell survival downstream of activation is the PI3K-AKT pathway. Our prior studies showed that the novel immunotherapeutic molecule T11-target structure (T11TS) blocks T-cell apoptosis in glioma. We also showed activation of immunological synapse components and calcineurin-NFAT pathway following T11TS immunotherapy of glioma-bearing rats...
June 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28494186/small-interference-itga6-gene-targeting-in-the-human-thymic-epithelium-differentially-regulates-the-expression-of-immunological-synapse-related-genes
#3
Daiane Cristina F Golbert, Eliane Santana-Van-Vliet, Marcelo Ribeiro-Alves, Marbella Maria B da Fonsêca, Ailin Lepletier, Daniella Arêas Mendes-da-Cruz, Guilherme Loss, Vinícius Cotta-de-Almeida, Ana Tereza R Vasconcelos, Wilson Savino
The thymus supports differentiation of T cell precursors. This process requires relocation of developing thymocytes throughout multiple microenvironments of the organ, mainly with thymic epithelial cells (TEC), which control intrathymic T cell differentiation influencing the formation and maintenance of the immunological synapse. In addition to the proteins of the major histocompatibility complex (MHC), this structure is supported by several adhesion molecules. During the process of thymopoiesis, we previously showed that laminin-mediated interactions are involved in the entrance of T-cell precursors into the thymus, as well as migration of differentiating thymocytes within the organ...
May 11, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28488245/chimeric-antigen-receptor-car-modified-natural-killer-cell-based-immunotherapy-and-immunological-synapse-formation-in-cancer-and-hiv
#4
REVIEW
Dongfang Liu, Shuo Tian, Kai Zhang, Wei Xiong, Ndongala Michel Lubaki, Zhiying Chen, Weidong Han
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use...
May 9, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28471021/syntaxin-4-mediates-endosome-recycling-for-lytic-granule-exocytosis-in-cytotoxic-t-lymphocytes
#5
Waldo A Spessott, Maria L Sanmillan, Vineet V Kulkarni, Margaret E McCormick, Claudio G Giraudo
Adaptive and innate immunity utilize the perforin-killing pathway to eliminate virus-infected or cancer cells. Cytotoxic T-lymphocytes (CTLs) and natural killer cells mediate this process by releasing toxic proteins at the contact area with target cells known as immunological synapse (IS). Formation of a stable IS and exocytosis of toxic proteins requires persistent fusion of Rab11a recycling endosomes with the plasma membrane (PM) that may assure the delivery of key effector proteins. Despite the importance of the recycling endosomal compartment, the membrane fusion proteins that control this process at the IS remain elusive...
May 4, 2017: Traffic
https://www.readbyqxmd.com/read/28452360/an-intermolecular-fret-sensor-detects-the-dynamics-of-t-cell-receptor-clustering
#6
Yuanqing Ma, Elvis Pandzic, Philip R Nicovich, Yui Yamamoto, Joanna Kwiatek, Sophie V Pageon, Aleš Benda, Jérémie Rossy, Katharina Gaus
Clustering of the T-cell receptor (TCR) is thought to initiate downstream signalling. However, the detection of protein clustering with high spatial and temporal resolution remains challenging. Here we establish a Förster resonance energy transfer (FRET) sensor, named CliF, which reports intermolecular associations of neighbouring proteins in live cells. A key advantage of the single-chain FRET sensor is that it can be combined with image correlation spectroscopy (ICS), single-particle tracking (SPT) and fluorescence lifetime imaging microscopy (FLIM)...
April 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28448002/measurement-of-t-cell-alloreactivity-using-imaging-flow-cytometry
#7
Stephen C Juvet, Sajad Moshkelgosha, Sharon Sanderson, Joanna Hester, Kathryn J Wood, Andrew Bushell
The measurement of immunological reactivity to donor antigens in transplant recipients is likely to be crucial for the successful reduction or withdrawal of immunosuppression. The mixed leukocyte reaction (MLR), limiting dilution assays, and trans-vivo delayed-type hypersensitivity (DTH) assay have all been applied to this question, but these methods have limited predictive ability and/or significant practical limitations that reduce their usefulness. Imaging flow cytometry is a technique that combines the multiparametric quantitative powers of flow cytometry with the imaging capabilities of fluorescent microscopy...
April 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28445761/live-cell-super-resolution-reveals-f-actin-and-plasma-membrane-dynamics-at-the-t-cell-synapse
#8
George W Ashdown, Garth L Burn, David J Williamson, Elvis Pandžić, Ruby Peters, Michael Holden, Helge Ewers, Lin Shao, Paul W Wiseman, Dylan M Owen
The cortical actin cytoskeleton has been shown to be critical for the reorganization and heterogeneity of plasma membrane components of many cells, including T cells. Building on previous studies at the T cell immunological synapse, we quantitatively assess the structure and dynamics of this meshwork using live-cell superresolution fluorescence microscopy and spatio-temporal image correlation spectroscopy. We show for the first time, to our knowledge, that not only does the dense actin cortex flow in a retrograde fashion toward the synapse center, but the plasma membrane itself shows similar behavior...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#9
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#10
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28367116/microglial-intracellular-ca-2-signaling-in-synaptic-development-and-its-alterations-in-neurodevelopmental-disorders
#11
REVIEW
Yoshito Mizoguchi, Akira Monji
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by deficits in social interaction, difficulties with language and repetitive/restricted behaviors. Microglia are resident innate immune cells which release many factors including proinflammatory cytokines, nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) when they are activated in response to immunological stimuli. Recent in vivo imaging has shown that microglia sculpt and refine the synaptic circuitry by removing excess and unwanted synapses and be involved in the development of neural circuits or synaptic plasticity thereby maintaining the brain homeostasis...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28366940/dock8-regulates-signal-transduction-events-to-control-immunity
#12
Conor J Kearney, Katrina L Randall, Jane Oliaro
Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome (AR-HIES), referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combined immunodeficiency disease (CID), clinically associated with chronic infections with diverse microbial pathogens, and a predisposition to malignancy. It is now becoming clear that DOCK8 regulates the function of diverse immune cell sub-types, particularly lymphocytes, to drive both innate and adaptive immune responses...
May 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28348273/cutting-edge-loss-of-t-cell-riam-precludes-conjugate-formation-with-apc-and-prevents-immune-mediated-diabetes
#13
Frederic Lagarrigue, Frank B Gertler, Mark H Ginsberg, Joseph M Cantor
Rap1-interacting adaptor molecule (RIAM) is a Rap1 effector that mediates the recruitment of talin to integrins, thereby supporting their activation. In this study, we investigated the role of RIAM in an adoptive transfer model for type I diabetes and report that RIAM expression in T cells is necessary for diabetes development. Loss of RIAM did not prevent lymphocyte recruitment to draining lymph nodes 24 h after transfer, but it was required for Ag-driven proliferation and cytotoxic killing. RIAM is recruited to immune synapses along with talin and LFA-1, and loss of RIAM profoundly suppresses Ag-dependent conjugate formation in primary naive and effector T cells...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28315353/crystal-structure-of-the-extracellular-domain-of-the-human-dendritic-cell-surface-marker-cd83
#14
Christiane S Heilingloh, Stefan Klingl, Claudia Egerer-Sieber, Benedikt Schmid, Sigrid Weiler, Petra Mühl-Zürbes, Jörg Hofmann, Joachim D Stump, Heinrich Sticht, Mirko Kummer, Alexander Steinkasserer, Yves A Muller
CD83 is a type-I membrane protein and an efficient marker for identifying mature dendritic cells. Whereas membrane-bound, full-length CD83 co-stimulates the immune system, a soluble variant (sCD83), consisting of the extracellular domain only, displays strong immune-suppressive activities. Besides a prediction that sCD83 adopts a V-set Ig-like fold, however, little is known about the molecular architecture of CD83 and the mechanism by which CD83 exerts its function on dendritic cells and additional immune cells...
April 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28292823/correction-annular-pip3-accumulation-controls-actin-architecture-and-modulates-cytotoxicity-at-the-immunological-synapse
#15
Audrey Le Floc'h, Yoshihiko Tanaka, Niels S Bantilan, Guillaume Voisinne, Grégoire Altan-Bonnet, Yoshinori Fukui, Morgan Huse
No abstract text is available yet for this article.
April 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28288102/a-fret-sensor-enables-quantitative-measurements-of-membrane-charges-in-live-cells
#16
Yuanqing Ma, Yui Yamamoto, Philip R Nicovich, Jesse Goyette, Jérémie Rossy, J Justin Gooding, Katharina Gaus
Membrane charge has a critical role in protein trafficking and signaling. However, quantification of the effective electrostatic potential of cellular membranes has remained challenging. We developed a fluorescence membrane charge sensor (MCS) that reports changes in the membrane charge of live cells via Förster resonance energy transfer (FRET). MCS is permanently attached to the inner leaflet of the plasma membrane and shows a linear, reversible and fast response to changes of the electrostatic potential...
April 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28255726/in-vivo-imaging-of-t-cell-immunological-synapses-and-kinapses-in-lymph-nodes
#17
Hélène D Moreau, Philippe Bousso
T cells can become activated in lymph nodes following a diverse set of interactions with antigen-presenting cells. These cellular contacts range from short and dynamic to stable and long-lasting interactions, termed kinapses and synapses, respectively. Here, we describe a methodology to generate naïve T cells expressing a fluorescent probe of interest through the generation of bone marrow chimeras and to image T cell dynamics using intravital two-photon microscopy. In these settings, the formation of kinapses and synapses can be triggered by the administration of low and high affinity peptides, respectively...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28255725/studying-the-immune-synapse-in-hiv-1-infection
#18
Iratxe Del Río-Iñiguez, Jérôme Bouchet, Andrés Alcover
T cells are the main cellular targets of the human immunodeficiency virus 1 (HIV-1). HIV-1 infection induces pleiotropic effects on the infected T cell that modify the T cell capacity to respond to antigen and facilitates virus replication. HIV-1 infection subverts the formation and function of the immunological synapse altering both actin cytoskeleton remodeling and intracellular vesicle traffic. We describe here our methods to unveil how HIV-1 and in particular its protein Nef modify vesicle traffic to the immunological synapse, perturbing the synapse activation capacity...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28255724/aberrant-immunological-synapses-driven-by-leukemic-antigen-presenting-cells
#19
Fabienne McClanahan Lucas, John G Gribben
Aberrant immune synapse formation between antigen-presenting and immune effector cells is a central mediator of immune dysfunction and can be observed across several haematologic malignancies. Here, we describe the cell preparation, conjugation and immune synapse quantification of B and T cells obtained from patients with leukaemia and the adaptions required when using cells from murine models of disease.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28255723/studying-the-t-cell-astrocyte-immune-synapse
#20
George P Cribaro, Elena Saavedra-López, Paola V Casanova, Laura Rodríguez, Carlos Barcia
In this chapter, we describe the technical details to visualize and analyze effector immunological synapses between T cells and astrocytes in the brain with high-resolution confocal imaging. This procedure is critical for the optimal and even penetration of labeling antibodies within the nerve tissue to obtain accurate staining and allow a uniform three-dimensional analysis of the T cell-astrocyte interactions. We emphasize here the comprehensive exploration of the tissue and analysis with confocal microscope as well as the display of microanatomical details of the three-dimensional reconstruction for interface visualization (including peripheral and central supramolecular activation clusters, effector molecules, and other organelles such as microtubule organizing centers (MTOCs) and Golgi apparatus)...
2017: Methods in Molecular Biology
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