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https://www.readbyqxmd.com/read/28214044/enhancement-of-antigen-specific-cd4-and-cd8-t-cell-responses-using-a-self-assembled-biologic-nanolipoprotein-particle-vaccine
#1
Dina Weilhammer, Alexis D Dunkle, Craig D Blanchette, Nicholas O Fischer, Michele Corzett, Doerte Lehmann, Tyler Boone, Paul Hoeprich, Adam Driks, Amy Rasley
To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. We utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4(+) and CD8(+) T cells in vitro compared to co-administration of free OVA and MPLA...
February 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28213500/inducible-t-cell-kinase-regulates-the-acquisition-of-cytolytic-capacity-and-degranulation-in-cd8-ctls
#2
Senta M Kapnick, Jane C Stinchcombe, Gillian M Griffiths, Pamela L Schwartzberg
Patients with mutations in inducible T cell kinase (ITK) are susceptible to viral infections, particularly EBV, suggesting that these patients have defective function of CD8(+) CTLs. In this study, we evaluated the effects of ITK deficiency on cytolysis in murine CTLs deficient in ITK, and both human and murine cells treated with an ITK inhibitor. We find that ITK deficiency leads to a global defect in the cytolysis of multiple targets. The absence of ITK both affected CTL expansion and delayed the expression of cytolytic effectors during activation...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28213366/tumor-infiltrating-and-peripheral-blood-t-cell-immunophenotypes-predict-early-relapse-in-localized-clear-cell-renal-cell-carcinoma
#3
Nicolas A Giraldo, Etienne Becht, Yann Vano, Florent Petitprez, Laetitia Lacroix, Pierre Validire, Rafael Sanchez-Salas, Alexandre Ingels, Stephane Marie Oudard, Audrey Moatti, Bénédicte Buttard, Sarah Bourras, Claire Germain, Xavier Cathelineau, Wolf-Herman Fridman, Catherine Sautes-Fridman
PURPOSE: The efficacy of PD-1 Checkpoint Blockade (ChB) as adjuvant therapy in localized clear cell Renal Cell Carcinoma (ccRCC) is currently unknown. The identification of tumor microenvironment (TME) prognostic biomarkers in this setting may help to define which patients could benefit from ChB and to uncover new therapeutic targets. EXPERIMENTAL DESIGN: We performed multiparametric flow cytometry immunophenotypic analysis of T cells isolated from tumor tissue (TIL), adjacent non-malignant renal tissue (RIL) and peripheral blood (PBL), in a cohort of patients (n=40) with localized ccRCC...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28212502/a-new-mechanism-shapes-the-na%C3%A3-ve-cd8-t-cell-repertoire-the-selection-for-full-diversity
#4
Pedro Gonçalves, Marco Ferrarini, Carmen Molina-Paris, Grant Lythe, Florence Vasseur, Annik Lim, Benedita Rocha, Orly Azogui
During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clone sizes...
February 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-upregulates-pd-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#5
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the TCR complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time points during treatment to assess cell presence in various organs as well as gene expression and cytokine production...
February 17, 2017: Immunology
https://www.readbyqxmd.com/read/28208397/impact-of-lipid-rafts-on-the-t-cell-receptor-and-peptide-major-histocompatibility-complex-interactions-under-different-measurement-conditions
#6
Long Li, Guang-Kui Xu, Fan Song
The interactions between T-cell receptor (TCR) and peptide-major-histocompatibility complex (pMHC), which enable T-cell development and initiate adaptive immune responses, have been intensively studied. However, a central issue of how lipid rafts affect the TCR-pMHC interactions remains unclear. Here, by using a statistical-mechanical membrane model, we show that the binding affinity of TCR and pMHC anchored on two apposing cell membranes is significantly enhanced because of the lipid raft-induced signaling protein aggregation...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28207945/cd4-cd25-garp-tregs-display-a-compromised-suppressive-function-in-patients-with-dilated-cardiomyopathy
#7
Yuzhen Wei, Kunwu Yu, Hui Wei, Xin Su, Ruirui Zhu, Huairui Shi, Haitao Sun, Quan Luo, Wenbin Xu, Junhui Xiao, Yucheng Zhong, Qiutang Zeng
Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein -A repetitions predominant (GARP) expressed on activated CD4(+) T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4(+) CD25(+) GARP(+) regulatory T cells (Tregs) in DCM. 45 DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral Th1 and Th17 number and their related cytokines (IFN-γ, IL-17), and an obvious decrease in Treg number, TGF-β1 levels and the expression of FOXP3 and GARP in patients with DCM as compared with controls...
February 16, 2017: Immunology
https://www.readbyqxmd.com/read/28203104/proton-magnetic-resonance-spectroscopy-assessment-of-metabolite-status-of-the-anterior-cingulate-cortex-in-chronic-pain-patients-and-healthy-controls
#8
Takahiro Ito, Sachiko Tanaka-Mizuno, Narihito Iwashita, Ikuo Tooyama, Akihiko Shiino, Katsuyuki Miura, Sei Fukui
BACKGROUND: Chronic pain is a common cause of reduced quality of life. Recent studies suggest that chronic pain patients have a different brain neurometabolic status to healthy people. Proton magnetic resonance spectroscopy ((1)H-MRS) can determine the concentrations of metabolites in a specific region of the brain without being invasive. PATIENTS AND METHODS: We recruited 56 chronic pain patients and 60 healthy controls to compare brain metabolic characteristics...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28203025/-trigemino-cardiac-reflex-in-skull-base-surgery
#9
H Z Duan, Y Zhang, L Li, J Y Zhang, Z Q Yi, S D Bao
OBJECTIVE: To explore the mechanism, clinical features, and prognosis of Trigemino-cardiac reflex (TCR) during skull base operations. METHODS: A retrospective analysis was performed on 291 patients with skull base disease from Jan. 2009 to Oct. 2015 in Peking University First Hospital. By reviewing the patients' operative data and anaesthetic electrical record, and we picked out all the patients who suffered from TCR during the operation and analyzed their surgical procedures, clinical features, influence factors, and prognosis...
February 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28202617/the-bacterial-peptidoglycan-sensing-molecules-nod1-and-nod2-promote-cd8-thymocyte-selection
#10
Marianne M Martinic, Irina Caminschi, Meredith O'Keeffe, Therese C Thinnes, Raelene Grumont, Steve Gerondakis, Dianne B McKay, David Nemazee, Amanda L Gavin
Nucleotide-binding and oligomerization domain (NOD)-like receptors NOD1 and NOD2 are cytosolic innate immune receptors that recognize microbial peptidoglycans. Although studies have addressed the role of NOD proteins in innate immune responses, little attention has been given to their impact on the developing adaptive immune system. We have assessed the roles of NOD1 and NOD2 deficiency on T cell development in mice. Our results demonstrate that NOD1 and NOD2 promote the positive selection/maturation of CD8 single-positive thymocytes in a thymocyte-intrinsic manner...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28199983/a-versatile-system-for-rapid-multiplex-genome-edited-car-t-cell-generation
#11
Jiangtao Ren, Xuhua Zhang, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Carl H June, Yangbing Zhao
The therapeutic potential of CRISPR system has already been demonstrated in many instances and begun to overlap with the rapidly expanding field of cancer immunotherapy, especially on the production of genetically modified T cell receptor or chimeric antigen receptor (CAR) T cells. Efficient genomic disruption of multiple gene loci to generate universal donor cells, as well as potent effector T cells resistant to multiple inhibitory pathways such as PD-1 and CTLA4 is an attractive strategy for cell therapy...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199938/assessment-of-multiple-exposure-to-chemical-elements-and-health-risks-among-residents-near-huodehong-lead-zinc-mining-area-in-yunnan-southwest-china
#12
Yirun Wang, Ruming Wang, Liyun Fan, Tiantian Chen, Yahong Bai, Qianru Yu, Ying Liu
The contents of chemical elements (Cd, Cr, Cu, Pb and Zn) in 11 kinds of crop/vegetables and soils around the Huodehong lead-zinc mining area in Yunnan, Southwest China were determined by using inductive coupled plasma emission spectrometry (ICP-MS). Results showed that element contents in soils decreased in the order of Zn > Pb > Cr > Cu > Cd. The high geo-accumulation indexes (Igeo) showed that cultivated soils near mine were practically polluted by Cd, Pb and Zn. The contents of Cd, Cr and Pb in crop/vegetables samples were significantly higher than the maximum permissible standard set by China...
January 12, 2017: Chemosphere
https://www.readbyqxmd.com/read/28197404/using-global-analysis-to-extend-the-accuracy-and-precision-of-binding-measurements-with-t-cell-receptors-and-their-peptide-mhc-ligands
#13
Sydney J Blevins, Brian M Baker
In cellular immunity, clonally distributed T cell receptors (TCRs) engage complexes of peptides bound to major histocompatibility complex proteins (pMHCs). In the interactions of TCRs with pMHCs, regions of restricted and variable diversity align in a structurally complex fashion. Many studies have used mutagenesis to attempt to understand the "roles" played by various interface components in determining TCR recognition properties such as specificity and cross-reactivity. However, these measurements are often complicated or even compromised by the weak affinities TCRs maintain toward pMHC...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#14
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196891/insights-into-immune-system-development-and-function-from-mouse-t-cell-repertoires
#15
Zachary Sethna, Yuval Elhanati, Chrissy S Dudgeon, Curtis G Callan, Arnold J Levine, Thierry Mora, Aleksandra M Walczak
The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195200/dynamical-footprint-of-cross-reactivity-in-a-human-autoimmune-t-cell-receptor
#16
Amit Kumar, Francesco Delogu
The present work focuses on the dynamical aspects of cross-reactivity between myelin based protein (MBP) self-peptide and two microbial peptides (UL15, PMM) for Hy.1B11 T-cell receptor (TCR). This same TCR was isolated from a patient suffering from multiple sclerosis (MS). The study aims at highlighting the chemical interactions underlying recognition mechanisms between TCR and the peptides presented by Major Histocompatibility Complex (MHC) proteins, which form a crucial component in adaptive immune response against foreign antigens...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194134/chronic-trigemino-cardiac-reflex-an-underestimated-truth
#17
REVIEW
Tumul Chowdhury, Bernhard Schaller
The trigemino-cardiac reflex (TCR) is a brainstem reflex that manifests as adverse cardiorespiratory events upon the stimulation of sensory branches of the fifth cranial nerve. This reflex is mainly investigated in different neurosurgical procedures and intervention. This reflex is commonly considered as an acute and mild physiological response. On the other hand, more devastating and chronic nature of this reflex is largely underreported and unknown. Therefore, this article aims to provide the comprehensive understanding of the chronic form of TCR, its manifestations, and management by literature search...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28193872/nf%C3%AE%C2%BAb-pim-1-eomesodermin-axis-is-critical-for-maintaining-cd8-t-cell-memory-quality
#18
Karin M Knudson, Curtis J Pritzl, Vikas Saxena, Amnon Altman, Mark A Daniels, Emma Teixeiro
T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193589/head-kidney-liver-and-skin-histopathology-and-gene-expression-in-gilthead-seabream-sparus-aurata-l-exposed-to-highly-polluted-marine-sediments-from-portman-bay-spain
#19
Said Ben Hamed, Francisco Guardiola, Alberto Cuesta, Salvadora Martínez, María José Martínez-Sánchez, Carmen Pérez-Sirvent, María Ángeles Esteban
Biomarkers have become crucial tools in modern environmental assessment as they can help to predict magnitude of pollution. The head-kidney (HK) and liver (hematopoietic and xenobiotic metabolism organs, respectively) are the key organs in all fish toxicological studies, although the skin has received less attention in this respect. The impact of two different types of polluted sediment collected from Portman Bay (Spain) on HK, liver and skin gene expression in gilthead seabream (Sparus aurata L.) exposed for two weeks to the sediments was determined by real time-PCR...
February 4, 2017: Chemosphere
https://www.readbyqxmd.com/read/28192730/inducible-turnover-of-optineurin-regulates-t-cell-activation
#20
Angela Montecalvo, Simon C Watkins, Jordan Orange, Lawrence P Kane
Optineurin (Optn) is an adaptor protein with homology to NF-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase (IKK) complex. Dysregulation of Optn has been linked to neurodegenerative, autoimmune and bone diseases. Optn shares a high degree of homology with NEMO, but is not part of the same high-molecular weight complex containing IKKα and IKKβ. Despite its homology with NEMO and the fact that it has been the subject of extensive study in several cell types, there are no published studies addressing the role of Optn during T cell activation...
February 10, 2017: Molecular Immunology
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