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self reactive T cell

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https://www.readbyqxmd.com/read/28530714/cd8%C3%AE-%C3%AE-intraepithelial-lymphocytes-arise-from-two-main-thymic-precursors
#1
Roland Ruscher, Rebecca L Kummer, You Jeong Lee, Stephen C Jameson, Kristin A Hogquist
TCRαβ(+)CD4(-)CD8α(+)CD8β(-) intestinal intraepithelial lymphocytes (CD8αα IELs) are an abundant population of thymus-derived T cells that protect the gut barrier surface. We sought to better define the thymic IEL precursor (IELp) through analysis of its maturation, localization and emigration. We defined two precursor populations among TCRβ(+)CD4(-)CD8(-) thymocytes by dependence on the kinase TAK1 and rigorous lineage-exclusion criteria. Those IELp populations included a nascent PD-1(+) population and a T-bet(+) population that accumulated with age...
May 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28491873/b-cd8-t-cell-interactions-in-the-anti-idiotypic-response-against-a-self-antibody
#2
Darel Martínez, Amaury Pupo, Lianet Cabrera, Judith Raymond, Nichol E Holodick, Ana María Hernández
P3 is a murine, germline, IgM mAb that recognizes N-glycolylated gangliosides and other self-antigens. This antibody is able to induce an anti-idiotypic IgG response and B-T idiotypic cascade, even in the absence of any adjuvant or carrier protein. P3 mAb immunization induces the expression of activation markers in a significant percentage of B-1a cells in vivo. Interestingly, transfer of both B-1a and B-2 to BALB/Xid mice was required to recover anti-P3 IgG response in this model. In fact, P3 mAb activated B-2 cells, in vitro, inducing secretion of IFN-γ and IL-4, although this activation was not detected ex vivo...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28467818/surrogate-wnt-agonists-that-phenocopy-canonical-wnt-and-%C3%AE-catenin-signalling
#3
Claudia Y Janda, Luke T Dang, Changjiang You, Junlei Chang, Wim de Lau, Zhendong A Zhong, Kelley S Yan, Owen Marecic, Dirk Siepe, Xingnan Li, James D Moody, Bart O Williams, Hans Clevers, Jacob Piehler, David Baker, Calvin J Kuo, K Christopher Garcia
Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28463230/cd1b-autoreactive-t-cells-contribute-to-hyperlipidemia-induced-skin-inflammation-in-mice
#4
Sreya Bagchi, Ying He, Hong Zhang, Liang Cao, Ildiko Van Rhijn, D Branch Moody, Johann E Gudjonsson, Chyung-Ru Wang
A large proportion of human T cells are autoreactive to group 1 CD1 proteins, which include CD1a, CD1b, and CD1c. However, the physiological role of the CD1 proteins remains poorly defined. Here, we have generated a double-transgenic mouse model that expresses human CD1b and CD1c molecules (hCD1Tg) as well as a CD1b-autoreactive TCR (HJ1Tg) in the ApoE-deficient background (hCD1Tg HJ1Tg Apoe-/- mice) to determine the role of CD1-autoreactive T cells in hyperlipidemia-associated inflammatory diseases. We found that hCD1Tg HJ1Tg Apoe-/- mice spontaneously developed psoriasiform skin inflammation characterized by T cell and neutrophil infiltration and a Th17-biased cytokine response...
May 2, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28459559/photostable-ratiometric-pdot-probe-for-in-vitro-and-in-vivo-imaging-of-hypochlorous-acid
#5
Li Wu, I-Che Wu, Christopher C DuFort, Markus A Carlson, Xu Wu, Lei Chen, Chun-Ting Kuo, Yuling Qin, Jiangbo Yu, Sunil R Hingorani, Daniel T Chiu
Developing probes for the detection of reactive oxygen species (ROS), a hallmark of many pathophysiological process, is imperative to both understanding the precise roles of ROS in many life-threatening diseases and optimizing therapeutic interventions. We herein report an all-in-one fluorescent semiconducting polymer based far-red to near-infrared (NIR) Pdot nanoprobe for the ratiometric detection of hypochlorous acid (HOCl). The fabrication takes the advantage of flexible polymer design by incorporating target-sensitive and target-inert fluorophores into a single conjugated polymer to avoid leakage or differential photobleaching problems existed in other nanoprobes...
May 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28456018/unique-features-in-the-presentation-of-insulin-epitopes-in-autoimmune-diabetes-an-update
#6
REVIEW
Xiaoxiao Wan, Emil R Unanue
Although an autoimmune disease involves diverse self-antigens, the initiation stage may require recognition of a limited number. This concept is verified in the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong evidence points to insulin as the prime antigen. The NOD mouse bears the I-A(g7) class II-MHC molecules (MHCII) that share common biochemical features and peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore, both NOD mice and patients with type 1 diabetes (T1D) display an early appearance of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell infiltration into the islets...
April 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28426686/reactive-oxygen-species-are-required-for-driving-efficient-and-sustained-aerobic-glycolysis-during-cd4-t-cell-activation
#7
Dana M Previte, Erin C O'Connor, Elizabeth A Novak, Christina P Martins, Kevin P Mollen, Jon D Piganelli
The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells...
2017: PloS One
https://www.readbyqxmd.com/read/28411807/a-sensitive-and-disposable-indium-tin-oxide-based-electrochemical-immunosensor-for-label-free-detection-of-mage-1
#8
Burçak Demirbakan, Mustafa Kemal Sezgintürk
MAGE-1 (MAGE, for melanoma antigen), was identified by virtue of its processing and cell surface expression as a tumor-specific peptide bound to major histocompatibility complexes which was reactive with autolytic T cells. 3-Glycidoxypropyltrimethoxysilane (3-GOPS) is frequently employed for the preparation of dense heterometal hybrid polymers which are used, e.g., for hard coatings of organic polymers and contact lens materials in the optical industry. In this study, we have improved a new immunological biosensor with indium tin oxide (ITO)...
July 1, 2017: Talanta
https://www.readbyqxmd.com/read/28362433/il-2-prevents-deletion-of-developing-t-regulatory-cells-in-the-thymus
#9
Daniel Y Hu, Rushika C Wirasinha, Christopher C Goodnow, Stephen R Daley
In the thymus, strongly self-reactive T cells may undergo apoptotic deletion or differentiate into Foxp3+ T-regulatory (T-reg) cells. Mechanisms that partition T cells into these two fates are unclear. Here, we show that IL-2 signalling is required to prevent deletion of CD4+ CD8- CCR7+ Helios+ thymocytes poised to upregulate Foxp3. The deletion prevented by IL-2 signalling is Foxp3 independent and occurs later in thymocyte development than the deletion that is prevented by Card11 signalling. Our results distinguish two bottlenecks at which strongly self-reactive thymocytes undergo deletion or progress to the next stage of T-reg differentiation; Card11 regulates the first bottleneck and IL-2 regulates the second...
June 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#10
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28335993/biomaterials-innovation-for-next-generation-ex%C3%A2-vivo-immune-tissue-engineering
#11
REVIEW
Ankur Singh
Primary and secondary lymphoid organs are tissues that facilitate differentiation of B and T cells, leading to the induction of adaptive immune responses. These organs are present in the body from birth and are also recognized as locations where self-reactive B and T cells can be eliminated during the natural selection process. Many insights into the mechanisms that control the process of immune cell development and maturation in response to infection come from the analysis of various gene-deficient mice that lack some or all hallmark features of lymphoid tissues...
June 2017: Biomaterials
https://www.readbyqxmd.com/read/28332095/identification-of-t-cell-target-antigens-in-glioblastoma-stem-like-cells-using-an-integrated-proteomics-based-approach-in-patient-specimens
#12
Carmen Rapp, Rolf Warta, Slava Stamova, Ali Nowrouzi, Christoph Geisenberger, Zoltan Gal, Saskia Roesch, Steffen Dettling, Simone Juenger, Mariana Bucur, Christine Jungk, Philip DaoTrong, Rezvan Ahmadi, Felix Sahm, David Reuss, Valentina Fermi, Esther Herpel, Volker Eckstein, Niels Grabe, Christoph Schramm, Markus A Weigand, Juergen Debus, Andreas von Deimling, Andreas Unterberg, Amir Abdollahi, Philipp Beckhove, Christel Herold-Mende
Glioblastoma (GBM) is a highly aggressive brain tumor and still remains incurable. Among others, an immature subpopulation of self-renewing and therapy-resistant tumor cells-often referred to as glioblastoma stem-like cells (GSCs)-has been shown to contribute to disease recurrence. To target these cells personalized immunotherapy has gained a lot of interest, e.g. by reactivating pre-existing anti-tumor immune responses against GSC antigens. To identify T cell targets commonly presented by GSCs and their differentiated counterpart, we used a proteomics-based separation of GSC proteins in combination with a T cell activation assay...
March 22, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28329691/myocardial-infarction-primes-autoreactive-t-cells-through-activation-of-dendritic-cells
#13
Katrien Van der Borght, Charlotte L Scott, Veronika Nindl, Ann Bouché, Liesbet Martens, Dorine Sichien, Justine Van Moorleghem, Manon Vanheerswynghels, Sofie De Prijck, Yvan Saeys, Burkhard Ludewig, Thierry Gillebert, Martin Guilliams, Peter Carmeliet, Bart N Lambrecht
Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28325685/a-positive-feedback-strategy-for-enhanced-chemotherapy-based-on-ros-triggered-self-accelerating-drug-release-nanosystem
#14
Jing-Jing Hu, Qi Lei, Meng-Yun Peng, Di-Wei Zheng, Yi-Xuan Chen, Xian-Zheng Zhang
Here, a positive feedback strategy was utilized to amplify the concentration of intracellular reactive oxygen species (ROS) and a ROS-triggered self-accelerating drug release nanosystem (defined as T/D@RSMSNs) was demonstrated for enhanced tumor chemotherapy. The mesoporous silica nanoparticles (MSNs) based nanocarriers were gated by β-cyclodextrin (β-CD) through the ROS-cleavable thioketal (TK) linker to encapsulate the anticancer drug doxorubicin hydrochloride (DOX) and ROS producing agent α-tocopheryl succinate (α-TOS), whose surface was further anchored with adamantane conjugated poly(ethylene glycol) chain (AD-PEG) via host-guest interaction...
March 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28300427/annexin-a1-as-a-target-for-managing-murine-pristane-induced-systemic-lupus-erythematosus
#15
Nikolina Mihaylova, Silviya Bradyanova, Petroslav Chipinski, Melinda Herbáth, Stela Chausheva, Dobroslav Kyurkchiev, József Prechl, Andrey I Tchorbanov
Systemic lupus erythematosus (SLE) is a polygenic pathological disorder which involves multiple organs. Self-specific B cells play a main role in the lupus pathogenesis by generating autoantibodies as well as by serving as important autoantigen-presenting cells. Autoreactive T lymphocytes, on the other hand, are responsible for B cell activation and proliferation, and cytokine production. Therefore, both factors promote the idea that a down-modulation of activated self-reactive T and B cells involved in the pathogenic immune response is a reasonable approach for SLE therapy...
March 16, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28298179/preparation-of-peptide-mhc-and-t-cell-receptor-dextramers-by-biotinylated-dextran-doping
#16
Michael T Bethune, Begoña Comin-Anduix, Yu-Hsien Hwang Fu, Antoni Ribas, David Baltimore
Peptide-major histocompatibility complex (pMHC) multimers enable the detection, characterization, and isolation of antigen-specific T-cell subsets at the single-cell level via flow cytometry and fluorescence microscopy. These labeling reagents exploit a multivalent scaffold to increase the avidity of individually weak T-cell receptor (TCR)-pMHC interactions. Dextramers are an improvement over the original streptavidin-based tetramer technology because they are more multivalent, improving sensitivity for rare, low-avidity T cells, including self/tumor-reactive clones...
March 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28295628/pathophysiological-aspects-of-red-blood-cells-in-end-stage-renal-disease-patients-resistant-to-recombinant-human-erythropoietin-therapy
#17
Hara T Georgatzakou, Vassilis L Tzounakas, Anastasios G Kriebardis, Athanassios D Velentzas, Effie G Papageorgiou, Artemis I Voulgaridou, Apostolos C Kokkalis, Marianna H Antonelou, Issidora S Papassideri
OBJECTIVE: Modified, bioreactive red blood cells (RBCs) and RBC-derived microvesicles (MVs) likely contribute to the hematological and cardiovascular complications in end-stage renal disease (ESRD). This study assesses the physiological profile of RBCs in patients with ESRD receiving standard or high doses of recombinant human erythropoietin (rhEPO). METHOD: Blood samples from twenty-eight patients under sustained hemodialysis, responsive, or not to standard rhEPO administration were examined for RBC morphology, fragility, hemolysis, redox status, removal signaling, membrane protein composition, and microvesiculation before and after dialysis...
March 10, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28286158/smith-magenis-syndrome-patients-often-display-antibody-deficiency-but-not-other-immune-pathologies
#18
Tiffany Perkins, Jacob M Rosenberg, Carole Le Coz, Joseph T Alaimo, Melissa Trofa, Sureni V Mullegama, Richard J Antaya, Soma Jyonouchi, Sarah H Elsea, Paul J Utz, Eric Meffre, Neil Romberg
BACKGROUND: Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder associated with recurrent otitis. Most SMS cases result from heterozygous interstitial chromosome 17p11.2 deletions that encompass not only the intellectual disability gene retinoic acid-induced 1 but also other genes associated with immunodeficiency, autoimmunity, and/or malignancy. OBJECTIVES: The goals of this study were to describe the immunological consequence of 17p11.2 deletions by determining the prevalence of immunological diseases in subjects with SMS and by assessing their immune systems via laboratory methods...
March 9, 2017: Journal of Allergy and Clinical Immunology in Practice
https://www.readbyqxmd.com/read/28273069/interplay-between-metabolic-identities-in-the-intestinal-crypt-supports-stem-cell-function
#19
Maria J Rodríguez-Colman, Matthias Schewe, Maaike Meerlo, Edwin Stigter, Johan Gerrits, Mia Pras-Raves, Andrea Sacchetti, Marten Hornsveld, Koen C Oost, Hugo J Snippert, Nanda Verhoeven-Duif, Riccardo Fodde, Boudewijn M T Burgering
The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5(+) crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5(+) CBCs and Paneth cells from the mouse small intestine display different metabolic programs...
March 8, 2017: Nature
https://www.readbyqxmd.com/read/28259946/%C3%AE-%C3%AE-tcr-immunoglobulin-constant-region-domain-exchange-in-human-%C3%AE-%C3%AE-tcrs-improves-tcr-pairing-without-altering-tcr-gene-modified-t-cell-function
#20
Changli Tao, Hongwei Shao, Wenfeng Zhang, Huaben Bo, Fenglin Wu, Han Shen, Shulin Huang
The adoptive genetic transfer of T cell receptors (TCRs) has been shown to be overall feasible and offer clinical potential as a treatment for different types of cancer. However, this promising clinical approach is limited by the serious potential consequence that exogenous TCR mispairing with endogenous TCR chains may lead to the risk of self-reactivity. In the present study, domain‑exchange and three‑dimensional modeling strategies were used to create a set of chimeric TCR variants, which were used to exchange the partial or complete constant region of αβTCR with corresponding γδTCR domains...
April 2017: Molecular Medicine Reports
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