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https://www.readbyqxmd.com/read/27920212/inhibition-of-antigen-specific-and-non-specific-stimulation-of-bovine-t-and-b-cells-by-lymphostatin-from-attaching-and-effacing-escherichia-coli
#1
Robin L Cassady-Cain, Elizabeth A Blackburn, Charlotte R Bell, Elizaveta Elshina, Jayne C Hope, Mark P Stevens
Enterohaemorrhagic E. coli (EHEC) and enteropathogenic E. coli (EPEC) are enteric bacterial pathogens of worldwide importance. Most EPEC and non-O157 EHEC strains express lymphostatin (also known as LifA), a chromosomally-encoded 365 kDa protein. We previously demonstrated that lymphostatin is a putative glycosyltransferase that is important in intestinal colonisation of cattle by EHEC serogroup O5, O111 and O26 strains. However, the nature and consequences of the interaction between lymphostatin and immune cells from the bovine host are ill-defined...
December 5, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27920091/interferon-gamma-limits-diabetogenic-cd8-t-cell-effector-responses-in-type-1-diabetes
#2
John P Driver, Jeremy J Racine, Cheng Ye, Deanna J Lamont, Brittney N Newby, Caroline G McPhee-Leeth, Harold D Chapman, Todd M Brusko, Yi-Guang Chen, Clayton E Mathews, David V Serreze
Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T-cells of IFNγ, generally considered a pro-inflammatory cytokine. However, IFNγ can also participate in tolerance induction pathways, indicating it is not solely pro-inflammatory. This study addresses how IFNγ can suppress activation of diabetogenic CD8(+) T-cells. CD8(+) T-cells transgenically expressing the diabetogenic AI4 T-cell receptor (TCR) adoptively transferred disease to otherwise unmanipulated NOD...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27920090/islet-derived-cd4-t-cells-targeting-proinsulin-in-human-autoimmune-diabetes
#3
Aaron W Michels, Laurie G Landry, Kristen A McDaniel, Liping Yu, Martha Campbell-Thompson, William W Kwok, Kenneth L Jones, Peter A Gottlieb, John W Kappler, Qizhi Tang, Bart O Roep, Mark A Atkinson, Clayton E Mathews, Maki Nakayama
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing beta cells within pancreatic islets. While insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T-cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T-cells from type 1 diabetes patients. We identified hundreds of T-cells from inflamed pancreatic islets of three young type 1 diabetes organ donors with a short disease duration with high risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27917914/t-cells-mediate-autoantibody-induced-cutaneous-inflammation-and-blistering-in-epidermolysis-bullosa-acquisita
#4
Katja Bieber, Mareike Witte, Shijie Sun, Jennifer E Hundt, Kathrin Kalies, Sören Dräger, Anika Kasprick, Trix Twelkmeyer, Rudolf A Manz, Peter König, Jörg Köhl, Detlef Zillikens, Ralf J Ludwig
T cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) - characterized and caused by autoantibodies targeting type VII collagen...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27914308/regulation-of-t-helper-cell-differentiation-by-e3-ubiquitin-ligases-and-deubiquitinating-enzymes
#5
REVIEW
Si-Fa Gao, Bo Zhong, Dandan Lin
CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively...
November 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27911793/heterogeneous-yet-stable-v%C3%AE-2-t-cell-profiles-define-distinct-cytotoxic-effector-potentials-in-healthy-human-individuals
#6
Paul L Ryan, Nital Sumaria, Christopher J Holland, Claire M Bradford, Natalia Izotova, Capucine L Grandjean, Ali S Jawad, Lesley A Bergmeier, Daniel J Pennington
Human γδ T cells display potent responses to pathogens and malignancies. Of particular interest are those expressing a γδ T-cell receptor (TCR) incorporating TCRδ-chain variable-region-2 [Vδ2((+))], which are activated by pathogen-derived phosphoantigens (pAgs), or host-derived pAgs that accumulate in transformed cells or in cells exposed to aminobisphosphonates. Once activated, Vδ2((+)) T cells exhibit multiple effector functions that have made them attractive candidates for immunotherapy. Despite this, clinical trials have reported mixed patient responses, highlighting a need for better understanding of Vδ2((+)) T-cell biology...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911407/preparation-of-cd4-t-cells-for-analysis-of-gd3-and-gd2-ganglioside-membrane-expression-by-microscopy
#7
Tania M Villanueva-Cabello, Iván Martinez-Duncker
The methods described herein for activation of naïve CD4(+) T cells in suspension and their adherence in coverslips for confocal microscopy analysis allow the spatial localization and visualization of gangliosides involved in CD4(+) T cell activation, that complement expression profiling experiments such as flow cytometry, western blotting or real-time PCR. The quantification of ganglioside expression through flow cytometry and their cellular localization through microscopy can be obtained by the use of anti-ganglioside antibodies with high affinity and specificity...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27911371/development-of-stem-cell-derived-antigen-specific-regulatory-t-cells-against-autoimmunity
#8
Mohammad Haque, Kristin Fino, Praneet Sandhu, Jianxun Song
Autoimmune diseases arise due to the loss of immunological self-tolerance. Regulatory T cells (Tregs) are important mediators of immunologic self-tolerance. Tregs represent about 5 - 10% of the mature CD4(+) T cell subpopulation in mice and humans, with about 1 - 2% of those Tregs circulating in the peripheral blood. Induced pluripotent stem cells (iPSCs) can be differentiated into functional Tregs, which have a potential to be used for cell-based therapies of autoimmune diseases. Here, we present a method to develop antigen (Ag)-specific Tregs from iPSCs (i...
November 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910998/aurora-a-shines-on-t-cell-activation-through-the-regulation-of-lck
#9
Noelia Blas-Rus, Eugenio Bustos-Morán, Noa B Martín-Cófreces, Francisco Sánchez-Madrid
Different protein kinases control signaling emanating from the T cell receptor (TCR) during antigen-specific T cell activation. Mitotic kinases, e.g. Aurora-A, have been widely studied in the context of mitosis due to their role during microtubule (MT) nucleation, becoming critical regulators of cell cycle progression. We have recently described a specific role for Aurora-A kinase in antigenic T cell activation. Blockade of Aurora-A in T cells severely disrupts the dynamics of MTs and CD3ζ-bearing signaling vesicles during T cell activation...
December 2, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27908754/cyclic-citrullinated-mbp87-99-peptide-stimulates-t-cell-responses-implications-in-triggering-disease
#10
Vasso Apostolopoulos, George Deraos, Minos-Timotheos Matsoukas, Stephanie Day, Lily Stojanovska, Theodore Tselios, Maria-Eleni Androutsou, John Matsoukas
Amino acid mutations to agonist peptide epitopes of myelin proteins have been used to modulate immune responses and experimental autoimmune encephalomyelitis (EAE, animal model of multiple sclerosis). Such amino acid alteration are termed, altered peptide ligands (APL). We have shown that the agonist myelin basic protein (MBP) 87-99 epitope (MBP87-99) with crucial T cell receptor (TCR) substitutions at positions 91 and 96 (K(91),P(96) (TCR contact residues) to R(91),A(96); [R(91),A(96)]MBP87-99) results in altered T cell responses and inhibits EAE symptoms...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27908640/flagellin-enhances-the-immunoprotection-of-formalin-inactivated-edwardsiella-tarda-vaccine-in-turbot
#11
Xiaohong Liu, Hua Zhang, Chenglong Jiao, Qin Liu, Yuanxing Zhang, Jingfan Xiao
Edwardsiella tarda is an important fish pathogen that causes extensive losses in farmed fish around the world. Various types of vaccines have been developed against E. tarda infection, such as inactivated vaccine, live attenuated vaccine and subunit vaccine. However, inactivated vaccine exhibits poor immune protection against edwardsiellosis in some reports. In this study, we aimed to evaluate the protective effect of formalin-killed cells (FKC) against E. tarda with flagellin, FlgD, as an adjuvant in turbot...
November 28, 2016: Vaccine
https://www.readbyqxmd.com/read/27903843/downregulation-of-l-arginine-metabolism-in-dendritic-cells-induces-tolerance-to-exogenous-antigen
#12
Patricia U Simioni, Luis Gr Fernandes, Wirla Msc Tamashiro
Dendritic cells (DC) are potential tools for therapeutic applications and several strategies to generate tolerogenic DCs are under investigation. When activated by cytokines and microbial products, DCs express mediators that modulate immune responses. In this regard, the metabolites generated by the activities of inducible nitric oxide synthase (iNOS) and arginase in DCs seem to play important roles. Here, we evaluated the effects of adoptive transfer of DCs generated in vitro from bone marrow precursors (BMDC) modulated with L-NAME (Nω-nitro-L-arginine methyl ester) and NOHA (NG-Hydroxy-L-arginine), inhibitors of iNOS and arginase, respectively, upon the immune response of the wild type (BALB/c) and OVA-TCR transgenic (DO11...
November 30, 2016: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/27903736/t-and-b-cell-markers-in-dried-blood-spots-of-neonates-with-congenital-cytomegalovirus-infection-b-cell-numbers-at-birth-are-associated-with-long-term-outcomes
#13
Roberta Rovito, Marjolein J Korndewal, Menno C van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C M Kroes, Anton W Langerak, Ann C T M Vossen
Congenital CMV infection (cCMV) is the most common congenital infection that can cause long-term impairment (LTI). The pathogenesis of LTI is not completely understood. Fetal immunity may play a role in controlling the infection and preventing LTI, although immune activation may also contribute to fetal immunopathology. In this study, we analyzed various molecular markers of T and B cell numbers in neonatal dried blood spots of 99 children with cCMV and 54 children without cCMV: δRec-ψJα signal joints on TCR excision circles, intron recombination signal sequence k-deleting element signal joints on Igκ-deleting recombination excision circles, genomic intron recombination signal sequence k-deleting element coding joint, genomic Vδ1-Jδ1, and Vδ2-Jδ1 rearrangements...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27903649/structural-mechanism-underpinning-cross-reactivity-of-a-cd8-t-cell-clone-that-recognises-a-peptide-derived-from-human-telomerase-reverse-transcriptase
#14
David K Cole, Hugo A van den Berg, Angharad Lloyd, Michael D Crowther, Konrad Beck, Julia Ekeruche-Makinde, John J Miles, Anna M Bulek, Garry Dolton, Andrea J Schauenburg, Aaron Wall, Anna Fuller, Mathew Clement, Bruno Laugel, Pierre J Rizkallah, Linda Wooldridge, Andrew K Sewell
T-cell cross-reactivity is essential for effective immune surveillance, but has also been implicated as a pathway to autoimmunity. Previous studies have demonstrated that T-cell receptors (TCRs) that focus on a minimal motif within the peptide are able to facilitate a high level of T-cell cross-reactivity. However, the structural database shows that most TCRs exhibit less focussed antigen binding involving contact with more peptide residues. To further explore the structural features that allow the clonally expressed TCR to functionally engage with multiple peptide-major histocompatibility complexes (pMHCs), we examined the ILA1 CD8+ T-cell clone that responds to a peptide sequence derived from human telomerase reverse transcriptase (hTERT)...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27900889/campylobacter-jejuni-strains-coresistant-to-tetracycline-and-ciprofloxacin-in-patients-with-gastroenteritis-in-croatia
#15
Merica Carev, Ana Kovačić, Anita Novak, Marija Tonkić, Ana Jerončić
BACKGROUND: Antibiotic-resistant Campylobacter jejuni strains are rapidly emerging worldwide. Here, we aimed to determine the antibiotic-resistance patterns and genetic structure of C. jejuni from stool samples of symptomatic patients in Dalmatia, the largest Croatian county. METHODS: In a population-based laboratory surveillance programme for campylobacteriosis in Dalmatia from May 2012 to May 2013, C. jejuni (n = 76) were collected from stool samples of all the patients hospitalized with gastroenteritis and matched positive outpatients (n = 77)...
November 30, 2016: Infectious Diseases
https://www.readbyqxmd.com/read/27900794/fast-and-efficient-free-induction-decay-mr-spectroscopic-imaging-of-the-human-brain-at-9-4-tesla
#16
Grzegorz L Chadzynski, Jonas Bause, Gunamony Shajan, Rolf Pohmann, Klaus Scheffler, Philipp Ehses
PURPOSE: The purpose of this work was to develop a fast and efficient MRSI-FID acquisition scheme and test its performance in vivo. The aim was to find a trade-off between the minimal total acquisition time and signal-to-noise ratio of the acquired spectra. METHODS: Measurements were performed on a 9.4 Tesla system. Sequence optimization included redesign of water suppression, optimization of the sequence gradients, and improvement of the sampling efficiency by minimizing the read-out time...
November 29, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/27899890/causal-role-of-thalamic-interneurons-in-brain-state-transitions-a-study-using-a-neural-mass-model-implementing-synaptic-kinetics
#17
Basabdatta Sen Bhattacharya, Thomas P Bond, Louise O'Hare, Daniel Turner, Simon J Durrant
Experimental studies on the Lateral Geniculate Nucleus (LGN) of mammals and rodents show that the inhibitory interneurons (IN) receive around 47.1% of their afferents from the retinal spiking neurons, and constitute around 20-25% of the LGN cell population. However, there is a definite gap in knowledge about the role and impact of IN on thalamocortical dynamics in both experimental and model-based research. We use a neural mass computational model of the LGN with three neural populations viz. IN, thalamocortical relay (TCR), thalamic reticular nucleus (TRN), to study the causality of IN on LGN oscillations and state-transitions...
2016: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#18
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein Kinase 2 (CK2) is a serine-threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899444/antigen-dependent-competition-shapes-the-local-repertoire-of-tissue-resident-memory-cd8-t-cells
#19
Andreas Muschaweckh, Veit R Buchholz, Anne Fellenzer, Christian Hessel, Paul-Albert König, Sha Tao, Ronny Tao, Mathias Heikenwälder, Dirk H Busch, Thomas Korn, Wolfgang Kastenmüller, Ingo Drexler, Georg Gasteiger
Tissue-resident memory CD8(+) T cells (TRM) constitute a major component of the immune-surveillance system in nonlymphoid organs. Local, noncognate factors are both necessary and sufficient to support the programming of TRM cell fate in tissue-infiltrating T cells. Recent evidence suggests that TCR signals received in infected nonlymphoid tissues additionally contribute to TRM cell formation. Here, we asked how antigen-dependent pathways influence the generation of skin-resident memory T cells that arise from a polyclonal repertoire of cells induced by infection with an antigenically complex virus and recombinant vaccine vector...
November 29, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27898263/genetic-alterations-affecting-gtpases-and-t-cell-receptor-signaling-in-peripheral-t-cell-lymphomas
#20
Rebecca L Boddicker, Gina L Razidlo, Andrew L Feldman
Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous tumors with poor response to standard therapy and few targeted treatments available. The identification of mutations in the T-cell receptor (TCR) signaling pathway that either directly or indirectly affect Ras- and Rho-family GTPases is an emerging theme across PTCL subtypes. This review summarizes the role of GTPases in TCR signaling and highlights the constellation of mutations in this pathway among PTCLs. In particular, focus is given to the functional impact of the mutations and opportunities for targeted therapy...
November 29, 2016: Small GTPases
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