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https://www.readbyqxmd.com/read/29332992/experiment-design-for-early-molecular-events-in-hiv-infection
#1
Aditya Jagarapu, LaMont Cannon, Ryan Zurakowski
The recent introduction of integrase inhibitors to the HIV antiviral repertoire permits us to create in vitro experiments that reliably terminate HIV infection at the point of chromosomal integration. This allows us to isolate the dynamics of a single round of infection, without needing to account for the influence of multiple overlapping rounds of infection. By measuring the various nucleic acid concentrations in a population of infected target cells at multiple time points, we can infer the rates of these molecular events with great accuracy, which allows us to compare the rates between target cells with different functional phenotypes...
May 2017: Proceedings of the ... American Control Conference
https://www.readbyqxmd.com/read/29331322/expression-level-of-risk-genes-of-mhc-class-ii-is-a-susceptibility-factor-for-autoimmunity-new-insights
#2
REVIEW
Carmen Gianfran, Laura Pisapia, Stefania Picascia, Maria Strazzullo, Giovanna Del Pozzo
To date, the study of the impact of major hystocompatibility complex on autoimmunity has been prevalently focused on structural diversity of MHC molecules in binding and presentation of (auto)antigens to cognate T cells. Recently, a number of experimental evidences suggested new points of view to investigate the complex relationships between MHC gene expression and the individual predisposition to autoimmune diseases. Irrespective of the nature of the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as a threshold of T cell receptors engaged is required, for the activation and proliferation of autoantigen-reactive T cells...
January 10, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29325279/-characteristics-of-igh-cdr3-repertoire-of-peripheral-b-cells-in-a-patient-with-primary-biliary-cholangitis-a-preliminary-study-using-high-throughput-sequencing
#3
D T Zhao, C L Guo, H P Yan, H Y Liao, Y M Liu, H P Zhang, L S An, C Y Huang, Y Han, Y Zhao
Objective: To analyze the characteristics of immunoglobulin heavy chain complementarity-determining region (IgH-CDR3) repertoire of peripheral B cells in a patient with primary biliary cholangitis (PBC) and to investigate the diversity of the immune system. Methods: Arm-PCR was used to amplify the IgH-CDR3 region of circulating B cells isolated from a PBC patient, and high-throughput sequencing was used to analyze the amplified product. The characteristics of immune repertoire were analyzed by bioinformatics...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29323662/crispr-cas9-based-genome-wide-screening-of-toxoplasma-gondii
#4
Saima M Sidik, Diego Huet, Sebastian Lourido
Apicomplexan parasites, such as Toxoplasma gondii, cause extensive morbidity and mortality in humans and livestock, highlighting the need for a deeper understanding of their molecular biology. Although techniques for the generation of targeted gene disruptions have long been available for apicomplexans, such methods are not readily scalable to the entire genome. We recently used CRISPR-Cas9 to disrupt all nuclear protein-coding genes in T. gondii using a pooled format. The method relies on transfection of a guide RNA library into parasites constitutively expressing Cas9...
January 2018: Nature Protocols
https://www.readbyqxmd.com/read/29298288/hierarchically-related-lineage-restricted-fates-of-multipotent-haematopoietic-stem-cells
#5
Joana Carrelha, Yiran Meng, Laura M Kettyle, Tiago C Luis, Ruggiero Norfo, Verónica Alcolea, Francesca Grasso, Adriana Gambardella, Amit Grover, Kari Högstrand, Allegra M Lord, Alejandra Sanjuan-Pla, Petter S Woll, Claus Nerlov, Jacobsen Sten Eirik W
Rare multipotent hematopoietic stem cells (HSCs) in adult bone marrow (BM) with extensive self-renewal potential possess the ability to efficiently replenish all myeloid and lymphoid blood cells1, securing long-term multilineage reconstitution following physiological and clinical challenges, including chemotherapy and hematopoietic transplantations2-4. HSC transplantation remains the only curative treatment for many hematological malignancies, but inefficient blood-lineage replenishment remains a major cause of morbidity and mortality5-6...
January 3, 2018: Nature
https://www.readbyqxmd.com/read/29296702/a-functional-dc-cross-talk-promotes-human-ilc-homeostasis-in-humanized-mice
#6
Silvia Lopez-Lastra, Guillemette Masse-Ranson, Oriane Fiquet, Sylvie Darche, Nicolas Serafini, Yan Li, Mathilde Dusséaux, Helene Strick-Marchand, James P Di Santo
Humanized mice harboring human hematopoietic systems offer a valuable small-animal model to assess human immune responses to infection, inflammation, and cancer. Human immune system (HIS) mice develop a broad repertoire of antigen receptor bearing B and T cells that can participate in adaptive immune responses after immunization. In contrast, analysis of innate immune components, including innate lymphoid cells (ILCs) and natural killer (NK) cells, is limited in current HIS mouse models, partly because of the poor development of these rare lymphoid subsets...
April 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289741/immune-monitoring-of-transplant-patients-in-transient-mixed-chimerism-tolerance-trials
#7
REVIEW
Megan Sykes
This review focuses on mechanistic studies performed in recipients of non-myeloablative bone marrow transplant regimens developed at Massachusetts General Hospital in HLA-identical and HLA-mismatched haploidentical combinations, initially as a platform for treatment of hematologic malignancies with immunotherapy in the form of donor leukocyte infusions, and later in combination with donor kidney transplantation for the induction of allograft tolerance. These studies point to a prominent early role for regulatory T cells in tolerance induction, followed by partial and gradual deletion of donor-reactive T cells...
December 28, 2017: Human Immunology
https://www.readbyqxmd.com/read/29288651/unopposed-il-36-activity-promotes-clonal-cd4-t-cell-responses-with-il-17a-production-in-generalized-pustular-psoriasis
#8
Akiko Arakawa, Sigrid Vollmer, Petra Besgen, Adrian Galinski, Burkhard Summer, Yoshio Kawakami, Andreas Wollenberg, Klaus Dornmair, Michael Spannagl, Thomas Ruzicka, Peter Thomas, Jörg C Prinz
Generalized pustular psoriasis (GPP) is the most severe psoriasis variant. Mutations in the IL-36 antagonist IL36RN, in CARD14 or AP1S3 provide genetic evidence for autoinflammatory aetiology but cannot explain its pathogenesis completely. Here we demonstrate that unopposed IL-36 signalling promotes antigen-driven and likely pathogenic T-helper 17 (Th17) responses in GPP. We observed that CD4+ T cells in blood and skin lesions of GPP patients were characterized by intense hyperproliferation, production of the GPP key mediator, IL-17A, and highly restricted T-cell receptor (TCR) repertoires with identical T-cell clones in blood and skin lesions indicating antigen-driven T-cell expansions...
December 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29288042/stat3-mutation-and-its-clinical-and-histopathologic-correlation-in-t-cell-large-granular-lymphocytic-leukemia
#9
Min Shi, Rong He, Andrew L Feldman, David S Viswanatha, Dragan Jevremovic, Dong Chen, William G Morice
Although T-cell large granular lymphocytic leukemia (T-LGLL) is a clinically indolent disorder, patients with moderate-to-severe cytopenia require therapeutic intervention. The recent discovery of STAT3 mutations has shed light on the genetic basis of T-LGLL pathogenesis. However, the association of STAT3 mutational status with patients' clinical, histopathologic, and other laboratory features has not been thoroughly evaluated in T-LGLL. In this study, STAT3 mutations were identified in 18 of 36 patients with T-LGLL (50%), including Y640F (12/18, 66...
December 26, 2017: Human Pathology
https://www.readbyqxmd.com/read/29282307/cutting-edge-low-affinity-tcrs-support-regulatory-t-cell-function-in-autoimmunity
#10
Maran L Sprouse, Ivan Shevchenko, Marissa A Scavuzzo, Faith Joseph, Thomas Lee, Samuel Blum, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3, suggesting distinct functional profiles...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29279323/the-hidden-genomic-and-transcriptomic-plasticity-of-giant-marker-chromosomes-in-cancer
#11
Gemma Macchia, Marco Severgnini, Stefania Purgato, Doron Tolomeo, Hilen Casciaro, Ingrid Cifola, Alberto L'Abbate, Anna Loverro, Orazio Palumbo, Massimo Carella, Laurence Bianchini, Giovanni Perini, Gianluca De Bellis, Fredrik Mertens, Mariano Rocchi, Clelia T Storlazzi
Genome amplification in the form of rings or giant rod-shaped marker chromosomes is a common genetic alteration in soft tissue tumours. The mitotic stability of these structures is often rescued by perfectly functioning analphoid neocentromeres, which therefore significantly contribute to cancer progression. Here, we disentangled the genomic architecture of many neocentromeres stabilizing marker chromosomes in well-differentiated liposarcoma and lung sarcomatoid carcinoma samples. In cells carrying heavily rearranged RGMs, these structures were assembled as patchworks of multiple short amplified sequences, disclosing an extremely high level of complexity and definitely ruling out the existence of regions prone to the neocentromere seeding...
December 26, 2017: Genetics
https://www.readbyqxmd.com/read/29275043/signatures-of-protein-expression-revealed-by-secretome-analyses-of-cancer-associated-fibroblasts-and-melanoma-cell-lines
#12
Tarcísio Liberato, Dayelle S Pessotti, Isabella Fukushima, Eduardo S Kitano, Solange M T Serrano, André Zelanis
The imbalance of cellular homeostasis during oncogenesis together with the high heterogeneity of tumor-associated stromal cells have a marked effect on the repertoire of the proteins secreted by malignant cells (the secretome). Hence, the study of tumoral secretomes provides insights for understanding the cross-talk between cells within the tumor microenvironment as well as the key effectors for the establishment of the pre-metastatic niche in distant tumor sites. In this context, we performed a proteomic analysis of the secretomes derived from four cell lines: a paired set of fibroblasts - Hs 895...
December 21, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29259996/phenotypic-and-functional-complexity-of-brain-infiltrating-t-cells-in-rasmussen-encephalitis
#13
Faiez Al Nimer, Ivan Jelcic, Christian Kempf, Tom Pieper, Herbert Budka, Mireia Sospedra, Roland Martin
Objective: To characterize the brain-infiltrating immune cell repertoire in Rasmussen encephalitis (RE) with special focus on the subsets, clonality, and their cytokine profile. Methods: The immune cell infiltrate of freshly isolated brain tissue from RE was phenotypically and functionally characterized using immunohistology, flow cytometry, and T-cell receptor (TCR) deep sequencing. Identification of clonally expanded T-cell clones (TCCs) was achieved by combining flow cytometry sorting of CD4+ and CD8+ T cells and high-throughput TCR Vβ-chain sequencing...
January 2018: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/29247824/high-throughput-sequencing-of-the-immune-repertoire-in-oncology-applications-for-clinical-diagnosis-monitoring-and-immunotherapies
#14
Baixin Ye, Daniel Smerin, Qingping Gao, Chunsheng Kang, Xiaoxing Xiong
The diagnostic, monitoring and therapeutic options for cancers currently remain limited. These limitations represent a large threat to human health. Adaptive immunity, which is dependent on diverse repertoires of B cell receptors (BCRs) and T cell receptors (TCRs), plays a critical role in the anti-tumor immune response. Modulation and surveillance of adaptive immunity has become a powerful weapon to combat cancers. Recently, the high-throughput sequencing of immune repertoire (HTS-IR) technology, which provides a robust tool for deep sequencing repertoires of BCRs or TCRs, has been applied in the development of tumor biomarkers and immunotherapeutics for cancers...
December 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29245903/deep-sequencing-of-the-t-cell-receptor-%C3%AE-repertoire-reveals-signature-patterns-and-clonal-drift-in-atherosclerotic-plaques-and-patients
#15
Zongwei Lin, Shao Qian, Yan Gong, Jianwei Ren, Lixia Zhao, Dongxiao Wang, Xiaowei Wang, Yun Zhang, Zhe Wang, Qunye Zhang
The T cell receptor (TCR) β repertoire directly reflects the status of T cell function. Meanwhile, the immune/inflammatory responses regulated by T cells are the critical determinants of atherosclerosis development. However, due to technical limitations, the composition and molecular characteristics of the TCR repertoire in atherosclerotic patients have not been fully elucidated. In the present study, we use powerful immune repertoire sequencing technology to study this issue. Results show that the utilization of V and/or J genes and the diversity of TCRβ repertoire in atherosclerotic plaques are significantly reduced compared to those in the peripheral blood of normal subjects and atherosclerotic patients...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29245286/case-report-for-recurrent-and-new-onset-sle-patients-treated-by-high-dose-glucocorticoid-therapy-characteristics-of-peripheral-tcr-beta-chain-cdr3-repertoires
#16
Jiang Yu, Bin Shi, Long Ma, Chunmei Liu, Suhong Sun, Rui Ma, Yuehong Qiu, Xinsheng Yao
RATIONALE: High-dose glucocorticoid therapy has been widely applied in clinical practice in systemic lupus erythematosus (SLE)patients, but less is known about the changes of T cells, especially the T cell receptor (TCR) repertoires, during the treatment. The aim of this paper is to describe the changes of TCR that recurrent and new-onset SLE patients treated by high-dose glucocorticoid therapy. PATIENT CONCERNS: Drugs of clinical treatment of SLE mainly include glucocorticoid, immunosuppressive agents, nonsteroidal anti-inflammatory drugs and B cell targeted drugs, etc, but the clinical symptoms were in remission and recurrent of onset patients with SLE...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29242851/in-depth-ptdins-3-4-5-p3-signalosome-analysis-identifies-dapp1-as-a-negative-regulator-of-gpvi-driven-platelet-function
#17
Tom N Durrant, James L Hutchinson, Kate J Heesom, Karen E Anderson, Len R Stephens, Phillip T Hawkins, Aaron J Marshall, Samantha F Moore, Ingeborg Hers
The class I phosphoinositide 3-kinase (PI3K) isoforms play important roles in platelet priming, activation, and stable thrombus formation. Class I PI3Ks predominantly regulate cell function through their catalytic product, the signaling phospholipid phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], which coordinates the localization and/or activity of a diverse range of binding proteins. Notably, the complete repertoire of these class I PI3K effectors in platelets remains unknown, limiting mechanistic understanding of class I PI3K-mediated control of platelet function...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29242513/scarf-1-promotes-adhesion-of-cd4-t-cells-to-human-hepatic-sinusoidal-endothelium-under-conditions-of-shear-stress
#18
Daniel A Patten, Sivesh K Kamarajah, Joanne M Rose, Joseph Tickle, Emma L Shepherd, David H Adams, Chris J Weston, Shishir Shetty
Liver-resident cells are constantly exposed to gut-derived antigens via portal blood and, as a consequence, they express a unique repertoire of scavenger receptors. Whilst there is increasing evidence that the gut contributes to chronic inflammatory liver disease, the role of scavenger receptors in regulating liver inflammation remains limited. Here, we describe for the first time the expression of scavenger receptor class F, member 1 (SCARF-1) on hepatic sinusoidal endothelial cells (HSEC). We report that SCARF-1 shows a highly localised expression pattern and co-localised with endothelial markers on sinusoidal endothelium...
December 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29241731/efficacy-of-lentiviral-mediated-gene-therapy-in-an-omenn-syndrome-rag2-mouse-model-is-not-hindered-by-inflammation-and-immune-dysregulation
#19
Valentina Capo, Maria Carmina Castiello, Elena Fontana, Sara Penna, Marita Bosticardo, Elena Draghici, Luigi P Poliani, Lucia Sergi Sergi, Rosita Rigoni, Barbara Cassani, Monica Zanussi, Paola Carrera, Paolo Uva, Kerry Dobbs, Nicolò Sacchetti, Luigi D Notarangelo, Niek P van Til, Gerard Wagemaker, Anna Villa
BACKGROUND: Omenn syndrome (OS) is a rare severe combined immunodeficiency associated with autoimmunity, caused by defects of the lymphoid-specific V(D)J recombination. Most patients carry hypomorphic mutations in recombination activating genes (RAG) 1 or 2. Hematopoietic stem cell (HSC) transplantation is the standard treatment, however gene therapy (GT) may represent a valid alternative, especially for patients lacking a matched donor. OBJECTIVE: To determine the efficacy of lentiviral vector (LV) mediated GT in the murine model of OS (Rag2R229Q/R229Q) in correcting immunodeficiency and autoimmunity...
December 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29238707/drug-repurposing-for-the-treatment-of-acute-myeloid-leukemia
#20
REVIEW
Vibeke Andresen, Bjørn T Gjertsen
Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature myeloid progenitor cells in the bone marrow, compromising of normal blood cell production and ultimately resulting in bone marrow failure. With a 20% overall survival rate at 5 years and 50% in the 18- to 65-year-old age group, new medicines are needed. It is proposed that development of repurposed drugs may be a part of the new therapy needed. AML is subdivided into recurrent molecular entities based on molecular genetics increasingly accessible for precision medicine...
2017: Frontiers in Medicine
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