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Immunological synapse

Wenli Zhu, Lili Tian, Xuanye Yue, Jingyi Liu, Ying Fu, Yaping Yan
Ischemic stroke induces profound effects on the peripheral immune system, which may participate the infectious complications. However, the exact function and mechanism of immune reaction in stroke development are not well-elucidated. Recently, several long non-coding RNAs (LncRNAs) are reported to affect ischemic stroke process, especially the immunological response after stroke. In the present study, we investigated the profile of LncRNAs in human ischemic stroke during the transition from the acute to subacute stage, when the state of the peripheral immune system changes from activation to systemic immunosuppression...
2019: Frontiers in Neurology
Hsiling Chiu, Preeti Trisal, Chad Bjorklund, Soraya Carrancio, Estela G Toraño, Carla Guarinos, Despoina Papazoglou, Patrick R Hagner, Asma Beldi-Ferchiou, Karin Tarte, Marie-Hélène Delfau-Larue, Franck Morschhauser, Alan G Ramsay, Anita K Gandhi
Chemotherapy plus rituximab has been the mainstay of treatment for follicular lymphoma (FL) for two decades but is associated with immunosuppression and relapse. In phase 2 studies, lenalidomide combined with rituximab (R2 ) has shown clinical synergy in front-line and relapsed/refractory FL. Here, we show that lenalidomide reactivated dysfunctional T and Natural Killer (NK) cells ex vivo from FL patients by enhancing proliferative capacity and T-helper cell type 1 (Th1) cytokine release. In combination with rituximab, lenalidomide improved antibody-dependent cellular cytotoxicity in sensitive and chemo-resistant FL cells, via a cereblon-dependent mechanism...
February 14, 2019: British Journal of Haematology
Veronica M Holmes, Carlos Maluquer de Motes, Paige T Richards, Jessenia Roldan, Arjun K Bhargava, Jordan S Orange, Claude Krummenacher
Regulation of Natural Killer (NK) cell activity is achieved by the integration of both activating and inhibitory signals acquired at the immunological synapse with potential target cells. NK cells express paired receptors from the immunoglobulin family which share common ligands from the nectin family of adhesion molecules. The activating receptor CD226 (DNAM-1) binds to nectin-2 and CD155, which are also recognized by the inhibitory receptor TIGIT. The third receptor in this family is CD96, which is less well characterized and may have different functions in human and mouse models...
2019: PloS One
Laura Gómez-Cabañas, Pilar López-Cotarelo, Olga Criado-García, Michael P Murphy, Patricia Boya, José Luis Rodríguez-Fernández
The immunological synapse (IS) is a superstructure formed during T cell activation at the zone of contact between T cells and dendritic cells (DCs). The IS includes specific molecular components in the T cell and DCs sides that may result in different functionality. Most of the studies on the IS have focused on the T cell side of this structure and, in contrast, the information available on the IS of DCs is sparse. Autophagy is a cellular process involved in the clearance of damaged proteins and organelles via lysosomal degradation...
February 4, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Kim S Friedmann, Monika Bozem, Markus Hoth
Amplitude and kinetics of intracellular Ca2+ signals ([Ca2+ ]int ) determine many immune cell functions. To mimic in vivo changes of [Ca2+ ]int in human immune cells, two approaches may be best suited: 1) Analyze primary human immune cells taken from blood under conditions resembling best physiological or pathophysiological conditions. 2.) Analyze the immune system in vivo or ex vivo in explanted tissue from small vertebrate animals, such as mice. With the help of genetically encoded Ca2+ indicators and intravital microscopy, [Ca2+ ]int have been investigated in murine T lymphocytes (T cells) in vivo during the last five years and in explanted lymph node (LN) during the last 10 years...
January 10, 2019: Seminars in Cell & Developmental Biology
Raquel Almansa, Leonor Nogales, Marta Martín-Fernández, Montse Batlle, Esther Villareal, Lucia Rico, Alicia Ortega, Guillermo López-Campos, David Andaluz-Ojeda, Paula Ramírez, Lorenzo Socias, Luis Tamayo, Jordi Vallés, Jesús F Bermejo-Martín, Ignacio Martín-Loeches
Background: Ventilator-associated pneumonia (VAP) is one of the most commonly encountered intensive care unit (ICU) acquired infections worldwide. The objective of the study was to identify the immune alteration occurring in patients suffering from VAP at the transcriptomic level and explore its potential use for clinical diagnoses of this disease. Methods: We performed a prospective observational study in five medical ICUs. Immunological gene expression profiles in the blood of VAP patients were compared with those of controls by using whole transcriptome microarrays and droplet digital polymerase chain reaction (ddPCR) in the first 24 hours following diagnosis...
November 2018: Annals of Translational Medicine
John A Hammer, Jia Wang, Mezida Saeed, Antonio Pedrosa
The engagement of aTcell with an antigen-presenting cell (APC) or activating surface results in the formation within the T cell of several distinct actin and actomyosin networks. These networks reside largely within a narrow zone immediately under the T cell's plasma membrane at its site of contact with the APC or activating surface, i.e., at the immunological synapse. Here we review the origin, organization, dynamics, and function of these synapse-associated actin and actomyosin networks. Importantly, recent insights into the nature of these actin-based cytoskeletal structures were made possible in several cases by advances in light microscopy...
December 21, 2018: Annual Review of Immunology
Miloš Knežević, Hongda Jiang, Shenshen Wang
Immune cells learn about their antigenic targets using tactile sense: a self-organized motif named immunological synapse forms between an immune cell and an antigen-presenting cell (APC) during recognition. Via synapses, immune cells apply mechanical pulling forces to selectively extract antigen (Ag) from APCs. Curiously, depending on its stage of development, a B lymphocyte exhibits distinct synaptic patterns and uses force at different strength and timing, which appears to strongly impact its ability to distinguish Ag affinities...
December 7, 2018: Physical Review Letters
Christian Peters, Annika Meyer, Léonce Kouakanou, Julia Feder, Tim Schricker, Marcus Lettau, Ottmar Janssen, Daniela Wesch, Dieter Kabelitz
TGF-β is a pleiotropic cytokine with multiple roles in immunity. Apart from its suppressive activity, TGF-β is a driving cytokine in the differentiation of induced regulatory T cells (iTreg) but also in the polarization of interleukin-9 (IL-9) producing T helper 9 (Th9) T cells. Human Vδ2 expressing γδ T cells exert potent cytotoxicity towards a variety of solid tumor and leukemia/lymphoma target cells and thus are in the focus of current strategies to develop cell-based immunotherapies. Here we report that TGF-β unexpectedly augments the cytotoxic effector activity of short-term expanded Vδ2 T cells when purified γδ T cells are activated with specific pyrophosphate antigens and IL-2 or IL-15 in the presence of TGF-β...
2019: Oncoimmunology
Bu-Nam Jeon, Hye-Ran Kim, Yun Shin Chung, Bo-Ra Na, Hyunkyung Park, Chorong Hong, Yasmin Fatima, Hyeonju Oh, Chang-Hyun Kim, Chang-Duk Jun
Correct temporal and spatial control of actin dynamics is essential for the cytotoxic T cell effector function against tumor cells. However, little is known whether actin engineering in tumor-targeted T cells can enhance their antitumor responses, thereby potentiating the adoptive T cell therapy. Here, we report that TAGLN2, a 22-KDa actin-stabilizing protein which is physically associated with lymphocyte function-associated antigen-1 (LFA-1), potentiates the OTI TCR CD8+ T cells to kill the intercellular adhesion molecule-1 (ICAM-1)-positive/OVA-presenting E0771 cells, but not ICAM-1-negative OVA-B16F10 cells, suggesting an 'inside-out' activation of LFA-1, which causes more efficient immunological synapse formation between T cells and tumor cells...
2018: Oncoimmunology
Patricia Castro-Sánchez, Rocío Ramirez-Munoz, Noa B Martín-Cófreces, Oscar Aguilar-Sopeña, Sergio Alegre-Gomez, Sara Hernández-Pérez, Raquel Reyes, Qi Zeng, Carlos Cabañas, Francisco Sánchez-Madrid, Pedro Roda-Navarro
The regulatory role of most dual specific phosphatases during T cell activation remains unknown. Here, we have studied the expression and function of phosphatases of regenerating liver (PRLs: PRL-1, PRL-2, and PRL-3) during T cell activation, as well as, the dynamic delivery of PRL-1 to the Immunological Synapse (IS). We found that T cell activation downregulates the expression of PRL-2, resulting in an increased PRL-1/PRL-2 ratio. PRL-1 redistributed at the IS in two stages: Initially, it was transiently accumulated at scanning membranes enriched in CD3 and actin, and at later times, it was delivered at the contact site from pericentriolar, CD3ζ-containing, vesicles...
2018: Frontiers in Immunology
Wei Ming Lim, Yuma Ito, Kumiko Sakata-Sogawa, Makio Tokunaga
The microtubule-organizing centre (MTOC) is repositioned to the centre of the contacted cell surface, the immunological synapse, during T cell activation. However, our understanding of its molecular mechanism remains limited. Here, we found that the microtubule plus-end tracking cytoplasmic linker protein 170 (CLIP-170) plays a novel role in MTOC repositioning using fluorescence imaging. Inhibition of CLIP-170 phosphorylation impaired both MTOC repositioning and interleukin-2 (IL-2) expression. T cell stimulation induced some fraction of dynein to colocalise with CLIP-170 and undergo plus-end tracking...
November 28, 2018: Scientific Reports
Chiara Beilin, Kaushik Choudhuri, Gerben Bouma, Dessislava Malinova, Jaime Llodra, David L Stokes, Motumu Shimaoka, Timothy A Springer, Michael L Dustin, Adrian J Thrasher, Siobhan O Burns
Background: Mutations of the common cytokine receptor gamma chain (γc) cause Severe Combined Immunodeficiency characterized by absent T and NK cell development. Although stem cell therapy restores these lineages, residual immune defects are observed that may result from selective persistence of γc-deficiency in myeloid lineages. However, little is known about the contribution of myeloid-expressed γc to protective immune responses.  Here we examine the importance of γc for myeloid dendritic cell (DC) function...
2018: Wellcome Open Research
Yong Gu Lee, Isaac Marks, Madduri Srinivasarao, Ananda Kumar Kanduluru, Sakkarapalayam M Mahalingam, Xin Liu, Haiyan Chu, Philip S Low
Most solid tumors are comprised of multiple clones that express orthogonal antigens, suggesting that novel strategies must be developed in order to adapt CAR T cell therapies to treat heterogeneous solid tumors. Here we utilized a cocktail of low molecular weight bispecific adapters, each comprised of fluorescein linked to a different tumor-specific ligand, to bridge between an anti-fluorescein CAR on the engineered T cell and a unique antigen on the cancer cell. This formation of an immunological synapse between the CAR T cell and cancer cell enabled use of a single anti-fluorescein CAR T cell to eradicate a diversity of antigenically different solid tumors implanted concurrently in NSG mice...
November 27, 2018: Cancer Research
Kyung-Ho Roh
Antigen-specific immunity conferred by T lymphocytes is a result of complex molecular interactions at the immunological synapse. A variety of biomimetic approaches have been devised to artificially induce T cell activation either to study the T cell biology or to expand and prime the therapeutic T cell populations. Here we first briefly review the molecular and cellular, structural and phenotypical bases that are involved in T cell activation. The artificial methods for T cell activation are then discussed in two grand categories, the soluble (3D) and the surface-anchored (2D) platforms with their design parameters...
2018: Advances in Experimental Medicine and Biology
Keisuke Watanabe, Shunichiro Kuramitsu, Avery D Posey, Carl H June
A major obstacle for chimeric antigen receptor (CAR) T cell therapy in solid tumors is the lack of truly tumor-specific target antigens, which translates to the targeting of tumor-associated antigens (TAAs) overexpressed on tumors but shared with normal organs, raising safety concerns. In addition, expression of TAAs in solid tumors is particularly heterogeneous. In this regard, it is critical to deeply understand the sensitivity of CAR T cells, especially against low-density targets and the possible therapeutic window of antigen density targeted by CAR T cells...
2018: Frontiers in Immunology
Zhi-Long Chen, Bei-Ni Gong, Qi-Long Wang, Zhi-Hui Xiao, Chong Deng, Wen-Qian Wang, Yingqiu Li
A primitive adaptive immune system has recently been suggested to be present in a basal chordate amphioxus (Branchiostoma belcheri, Bb), making it an ideal model for studying the origin of adaptive immune. The novel protein kinase C isoform PKC-θ, but not its closest isoform PKC-δ, plays a critical role for mammalian T-cell activation via translocation to immunological synapse (IS) mediated by a unique PKC-θ V3 domain containing one PxxP motif. To understand the evolution of this unique PKC-θ V3 domain and the primitive adaptive immune system in amphioxus, we comparatively studied the orthologs of PKC-δ and -θ from amphioxus and other species...
January 2019: Fish & Shellfish Immunology
Manpreet Kaur, Dhaneshwar Kumar, Vincent Butty, Sudhakar Singh, Alexandre Esteban, Gerald R Fink, Hidde L Ploegh, Sharvan Sehrawat
To gain insights into the molecular mechanisms and pathways involved in the activation of γ-herpesvirus (MHV68)-specific T cell receptor transnuclear (TN) CD8+ T cells, we performed a comprehensive transcriptomic analysis. Upon viral infection, we observed differential expression of several thousand transcripts encompassing various networks and pathways in activated TN cells compared with their naive counterparts. Activated cells highly upregulated galectin-3. We therefore explored the role of galectin-3 in influencing anti-MHV68 immunity...
October 17, 2018: iScience
James Muller, Audrey Baeyens, Michael L Dustin
The tumor necrosis factor receptor superfamily (TNFRSF) and their ligands mediate lymphoid tissue development and homeostasis in addition to key aspects of innate and adaptive immune responses. T cells of the adaptive immune system express a number of TNFRSF members that are used to receive signals at different instructive stages and produce several tumor necrosis factor superfamily (TNFSF) members as effector molecules. There is also one example of a TNFRSF member serving as a ligand for negative regulatory checkpoint receptors...
2018: Advances in Immunology
Marjolein B M Meddens, Svenja F B Mennens, F Burcu Celikkol, Joost Te Riet, Johannes S Kanger, Ben Joosten, J Joris Witsenburg, Roland Brock, Carl G Figdor, Alessandra Cambi
Activation of the T cell receptor (TCR) on the T cell through ligation with antigen-MHC complex of an antigen-presenting cell (APC) is an essential process in the activation of T cells and induction of the subsequent adaptive immune response. Upon activation, the TCR, together with its associated co-receptor CD3 complex, assembles in signaling microclusters that are transported to the center of the organizational structure at the T cell-APC interface termed the immunological synapse (IS). During IS formation, local cell surface receptors and associated intracellular molecules are reorganized, ultimately creating the typical bull's eye-shaped pattern of the IS...
2018: Frontiers in Immunology
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