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https://www.readbyqxmd.com/read/28732506/new-insights-into-blimp-1-in-t-lymphocytes-a-divergent-regulator-of-cell-destiny-and-effector-function
#1
REVIEW
Shin-Huei Fu, Li-Tzu Yeh, Chin-Chen Chu, B Lin-Ju Yen, Huey-Kang Sytwu
B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3(+) regulatory T cells with an effector phenotype...
July 21, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28681703/hybrid-approach-to-model-the-spatial-regulation-of-t-cell-responses
#2
Anass Bouchnita, Gennady Bocharov, Andreas Meyerhans, Vitaly Volpert
BACKGROUND: Moving from the molecular and cellular level to a multi-scale systems understanding of immune responses requires the development of novel approaches to integrate knowledge and data from different biological levels into mechanism-based integrative mathematical models. The aim of our study is to present a methodology for a hybrid modelling of immunological processes in their spatial context. METHODS: A two-level hybrid mathematical model of immune cell migration and interaction integrating cellular and organ levels of regulation for a 2D spatial consideration of idealized secondary lymphoid organs is developed...
June 21, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28659925/immune-checkpoint-function-of-cd85j-in-cd8-t-cell-differentiation-and-aging
#3
Claire E Gustafson, Qian Qi, Jessica Hutter-Saunders, Sheena Gupta, Rohit Jadhav, Evan Newell, Holden Maecker, Cornelia M Weyand, Jörg J Goronzy
Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648661/de-novo-epigenetic-programs-inhibit-pd-1-blockade-mediated-t-cell-rejuvenation
#4
Hazem E Ghoneim, Yiping Fan, Ardiana Moustaki, Hossam A Abdelsamed, Pradyot Dash, Pranay Dogra, Robert Carter, Walid Awad, Geoff Neale, Paul G Thomas, Ben Youngblood
Immune-checkpoint-blockade (ICB)-mediated rejuvenation of exhausted T cells has emerged as a promising approach for treating various cancers and chronic infections. However, T cells that become fully exhausted during prolonged antigen exposure remain refractory to ICB-mediated rejuvenation. We report that blocking de novo DNA methylation in activated CD8 T cells allows them to retain their effector functions despite chronic stimulation during a persistent viral infection. Whole-genome bisulfite sequencing of antigen-specific murine CD8 T cells at the effector and exhaustion stages of an immune response identified progressively acquired heritable de novo methylation programs that restrict T cell expansion and clonal diversity during PD-1 blockade treatment...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28622514/landscape-of-infiltrating-t-cells-in-liver-cancer-revealed-by-single-cell-sequencing
#5
Chunhong Zheng, Liangtao Zheng, Jae-Kwang Yoo, Huahu Guo, Yuanyuan Zhang, Xinyi Guo, Boxi Kang, Ruozhen Hu, Julie Y Huang, Qiming Zhang, Zhouzerui Liu, Minghui Dong, Xueda Hu, Wenjun Ouyang, Jirun Peng, Zemin Zhang
Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28617941/association-of-immunoglobulin-g4-and-free-light-chain-with-idiopathic-pleural-effusion
#6
Y Murata, K Aoe, Y Mimura-Kimura, T Murakami, K Oishi, T Matsumoto, H Ueoka, K Matsunaga, M Yano, Y Mimura
The cause of pleural effusion remains uncertain in approximately 15% of patients despite exhaustive evaluation. As recently described immunoglobulin (Ig)G4-related disease is a fibroinflammatory disorder that can affect various organs, including the lungs, we investigate whether idiopathic pleural effusion includes IgG4-associated etiology. Between 2000 and 2012, we collected 830 pleural fluid samples and reviewed 35 patients with pleural effusions undiagnosed after pleural biopsy at Yamaguchi-Ube Medical Center...
October 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21-low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#7
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B-cell receptor (BCR), such as high expression of phosphorylated extracellular signal-regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion, such as CD21(low) phenotype and a defective response to ligation of BCR and Toll-like receptor 9 (TLR9). MC usually regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28225754/targeting-a-car-to-the-trac-locus-with-crispr-cas9-enhances-tumour-rejection
#8
Justin Eyquem, Jorge Mansilla-Soto, Theodoros Giavridis, Sjoukje J C van der Stegen, Mohamad Hamieh, Kristen M Cunanan, Ashlesha Odak, Mithat Gönen, Michel Sadelain
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies. CARs are typically transduced into the T cells of a patient using γ-retroviral vectors or other randomly integrating vectors, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing...
March 2, 2017: Nature
https://www.readbyqxmd.com/read/28103239/identifying-t-cell-receptors-from-high-throughput-sequencing-dealing-with-promiscuity-in-tcr%C3%AE-and-tcr%C3%AE-pairing
#9
Edward S Lee, Paul G Thomas, Jeff E Mold, Andrew J Yates
Characterisation of the T cell receptors (TCR) involved in immune responses is important for the design of vaccines and immunotherapies for cancer and autoimmune disease. The specificity of the interaction between the TCR heterodimer and its peptide-MHC ligand derives largely from the juxtaposed hypervariable CDR3 regions on the TCRα and TCRβ chains, and obtaining the paired sequences of these regions is a standard for functionally defining the TCR. A brute force approach to identifying the TCRs in a population of T cells is to use high-throughput single-cell sequencing, but currently this process remains costly and risks missing small clones...
January 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28073550/growth-and-bioactive-secondary-metabolites-of-arctic-protoceratium-reticulatum-dinophyceae
#10
Manuel Sala-Pérez, Tilman J Alpermann, Bernd Krock, Urban Tillmann
Harmful algal blooms are mainly caused by marine dinoflagellates and are known to produce potent toxins that may affect the ecosystem, human activities and health. Such events have increased in frequency and intensity worldwide in the past decades. Numerous processes involved in Global Change are amplified in the Arctic, but little is known about species specific responses of arctic dinoflagellates. The aim of this work was to perform an exhaustive morphological, phylogenetical and toxinological characterization of Greenland Protoceratium reticulatum and, in addition, to test the effect of temperature on growth and production of bioactive secondary metabolites...
May 2016: Harmful Algae
https://www.readbyqxmd.com/read/28068406/superclone-expansion-long-distance-clonal-dispersal-and-local-genetic-structuring-in-the-coral-pocillopora-damicornis-type-%C3%AE-in-reunion-island-south-western-indian-ocean
#11
Pauline Gélin, Cécile Fauvelot, Vincent Mehn, Sophie Bureau, Héloïse Rouzé, Hélène Magalon
The scleractinian coral Pocillopora damicornis type β is known to present a mixed reproduction mode: through sexual reproduction, new genotypes are created, while asexual reproduction insures their propagation. In order to investigate the relative proportion of each reproduction mode in P. damicornis type β populations from Reunion Island, Indian Ocean, clonal propagation along the west coast was assessed through four sampling sites with increasing geographical distance between sites. Coral colonies were sampled either exhaustively, randomly or haphazardly within each site, and genotypic diversity was assessed using 13 microsatellite loci over a total of 510 P...
2017: PloS One
https://www.readbyqxmd.com/read/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#12
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi, Kimon V Argyropoulos, Gertrude Gunset, Fabiana Perna, Fabiana M Kreines, Emily R Levy, Sophie Lieberman, Hillary V Jay, Andrea Z Tuckett, Johannes L Zakrzewski, Lisa Tan, Lauren F Young, Kate Takvorian, Jarrod A Dudakov, Robert R Jenq, Alan M Hanash, Ana Carolina F Motta, George F Murphy, Chen Liu, Andrea Schietinger, Michel Sadelain, Marcel R M van den Brink
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies...
February 2017: Nature Medicine
https://www.readbyqxmd.com/read/27861555/p16ink4a-expression-and-immunologic-aging-in-chronic-hiv-infection
#13
Susan Pereira Ribeiro, Jeffrey M Milush, Edecio Cunha-Neto, Esper G Kallas, Jorge Kalil, Luiz Felipe D Passero, Peter W Hunt, Steven G Deeks, Douglas F Nixon, Devi SenGupta
Chronic HIV infection is characterized by increased immune activation and immunosenescence. p16 INK4a (p16) is a member of the cyclin-dependent kinase antagonist family that inhibits cellular proliferation, and its protein expression increases during normal chronological aging. However, some infectious diseases can increase the expression of this anti-proliferative protein, potentially accelerating immunological aging and dysfunction. In order to investigate the immunological aging in HIV patients, p16 protein expression was evaluated by flow cytometry, in T cell subsets in a cohort of chronically HIV-infected patients on and off ART as well as age-matched healthy controls...
2016: PloS One
https://www.readbyqxmd.com/read/27570067/rna-splicing-modulation-selectively-impairs-leukemia-stem-cell-maintenance-in-secondary-human-aml
#14
Leslie A Crews, Larisa Balaian, Nathaniel P Delos Santos, Heather S Leu, Angela C Court, Elisa Lazzari, Anil Sadarangani, Maria A Zipeto, James J La Clair, Reymundo Villa, Anna Kulidjian, Rainer Storb, Sheldon R Morris, Edward D Ball, Michael D Burkart, Catriona H M Jamieson
Age-related human hematopoietic stem cell (HSC) exhaustion and myeloid-lineage skewing promote oncogenic transformation of hematopoietic progenitor cells into therapy-resistant leukemia stem cells (LSCs) in secondary acute myeloid leukemia (AML). While acquisition of clonal DNA mutations has been linked to increased rates of secondary AML for individuals older than 60 years, the contribution of RNA processing alterations to human hematopoietic stem and progenitor aging and LSC generation remains unclear. Comprehensive RNA sequencing and splice-isoform-specific PCR uncovered characteristic RNA splice isoform expression patterns that distinguished normal young and aged human stem and progenitor cells (HSPCs) from malignant myelodysplastic syndrome (MDS) and AML progenitors...
November 3, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27466420/demethylation-of-the-pd-1-promoter-is-imprinted-during-the-effector-phase-of-cd8-t-cell-exhaustion
#15
Eunseon Ahn, Ben Youngblood, Junghwa Lee, Judong Lee, Surojit Sarkar, Rafi Ahmed
UNLABELLED: PD-1 is an inhibitory receptor that has a major role in T cell dysfunction during chronic infections and cancer. While demethylation of the PD-1 promoter DNA is observed in exhausted T cells isolated from chronically infected individuals, little is known about when this stable demethylation of PD-1 promoter DNA is programmed during the course of a chronic infection. To assess if PD-1 promoter DNA demethylation is impacted by prolonged stimulation during effector phase of chronic infection, we adoptively transferred virus-specific day 8 effector CD8 T cells from mice infected with lymphocytic choriomeningitis virus (LCMV) clone 13 into recipient mice that had cleared an acute infection...
October 1, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27190719/genome-scale-investigation-of-phenotypically-distinct-but-nearly-clonal-trichoderma-strains
#16
Claudia Lange, Richard J Weld, Murray P Cox, Rosie E Bradshaw, Kirstin L McLean, Alison Stewart, Johanna M Steyaert
Biological control agents (BCA) are beneficial organisms that are applied to protect plants from pests. Many fungi of the genus Trichoderma are successful BCAs but the underlying mechanisms are not yet fully understood. Trichoderma cf. atroviride strain LU132 is a remarkably effective BCA compared to T. cf. atroviride strain LU140 but these strains were found to be highly similar at the DNA sequence level. This unusual combination of phenotypic variability and high DNA sequence similarity between separately isolated strains prompted us to undertake a genome comparison study in order to identify DNA polymorphisms...
2016: PeerJ
https://www.readbyqxmd.com/read/27183600/the-hayflick-limit-may-determine-the-effective-clonal-diversity-of-naive-t-cells
#17
Wilfred Ndifon, Jonathan Dushoff
Having a large number of sufficiently abundant T cell clones is important for adequate protection against diseases. However, as shown in this paper and elsewhere, between young adulthood and >70 y of age the effective clonal diversity of naive CD4/CD8 T cells found in human blood declines by a factor of >10. (Effective clonal diversity accounts for both the number and the abundance of T cell clones.) The causes of this observation are incompletely understood. A previous study proposed that it might result from the emergence of certain rare, replication-enhancing mutations in T cells...
June 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27161713/po-26-whole-blood-rotational-thromboelastometry-rotem-to-detect-hypercoagulability-in-patients-with-myeloproliferative-neoplasms-mpn
#18
C Giaccherini, C Verzeroli, M Marchetti, S Gamba, F Piras, L Russo, S Tessarolo, A Vignoli, G Finazzi, A Rambaldi, A Falanga
INTRODUCTION: Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are two MPNs characterized by a "clonal" overproduction of one or more blood cell lines, hypercoagulability, and an increased incidence of thrombosis. ROTEM is a point of care global coagulation assay performed in whole blood, able to evaluate platelets and fibrinogen contributions to the clotting process. Until now few studies evaluated the thromboelastometry profile of MPN patients. AIM: This study assess the feasibility of using ROTEM to characterize the prothrombotic state of MPN patients and to evaluate whether the thromboelastometry profile varies according to mutational status and/or treatment, and is influenced by hemocromocytometric parameters...
April 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27124452/dissecting-the-multicellular-ecosystem-of-metastatic-melanoma-by-single-cell-rna-seq
#19
Itay Tirosh, Benjamin Izar, Sanjay M Prakadan, Marc H Wadsworth, Daniel Treacy, John J Trombetta, Asaf Rotem, Christopher Rodman, Christine Lian, George Murphy, Mohammad Fallahi-Sichani, Ken Dutton-Regester, Jia-Ren Lin, Ofir Cohen, Parin Shah, Diana Lu, Alex S Genshaft, Travis K Hughes, Carly G K Ziegler, Samuel W Kazer, Aleth Gaillard, Kellie E Kolb, Alexandra-Chloé Villani, Cory M Johannessen, Aleksandr Y Andreev, Eliezer M Van Allen, Monica Bertagnolli, Peter K Sorger, Ryan J Sullivan, Keith T Flaherty, Dennie T Frederick, Judit Jané-Valbuena, Charles H Yoon, Orit Rozenblatt-Rosen, Alex K Shalek, Aviv Regev, Levi A Garraway
To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase...
April 8, 2016: Science
https://www.readbyqxmd.com/read/27102208/multiple-myeloma-causes-clonal-t-cell-immunosenescence-identification-of-potential-novel-targets-for-promoting-tumour-immunity-and-implications-for-checkpoint-blockade
#20
H Suen, R Brown, S Yang, C Weatherburn, P J Ho, N Woodland, N Nassif, P Barbaro, C Bryant, D Hart, J Gibson, D Joshua
Tumour-induced dysfunction of cytotoxic T cells in patients with multiple myeloma (MM) may contribute to immune escape and be responsible for the lack of therapeutic efficacy of immune checkpoint blockade. We therefore investigated dysfunctional clonal T cells in MM and demonstrated immunosenescence but not exhaustion as a predominant feature. T-cell clones were detected in 75% of MM patients and their prognostic significance was revalidated in a new post-immunomodulatory drug cohort. The cells exhibited a senescent secretory effector phenotype: KLRG-1+/CD57+/CD160+/CD28-...
August 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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