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Journal of Immunology: Official Journal of the American Association of Immunologists

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https://www.readbyqxmd.com/read/28446568/lis1-regulates-germinal-center-b-cell-antigen-acquisition-and-affinity-maturation
#1
Jingjing Chen, Zhenming Cai, Le Zhang, Yuye Yin, Xufeng Chen, Chao Chen, Yang Zhang, Sulan Zhai, Xuehui Long, Xiaolong Liu, Xiaoming Wang
The germinal center (GC) is the site where activated B cells undergo rapid expansions, somatic hypermutation, and affinity maturation. Affinity maturation is a process of Ag-driven selection. The amount of Ag acquired and displayed by GC B cells determines whether it can be positively selected, and therefore Ag acquisition has to be tightly regulated to ensure the efficient affinity maturation. Cell expansion provides sufficient quantity of GC B cells and Abs, whereas affinity maturation improves the quality of Abs...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28446567/determination-of-a-key-antigen-for-immunological-intervention-to-target-the-latent-stage-of-toxoplasma-gondii
#2
Qila Sa, Eri Ochiai, Ashish Tiwari, Jeremi Mullins, Nilabh Shastri, Corinne Mercier, Marie-France Cesbron-Delauw, Yasuhiro Suzuki
Toxoplasma gondii, an obligate intracellular protozoan parasite, establishes a chronic infection by forming cysts preferentially in the brain. Up to one third of the human population worldwide is estimated to be chronically infected with this parasite. However, there is currently no drug effective against the cyst form of the parasite. In addition, the protective immunity against the cysts remains largely unknown. We analyzed the molecular mechanisms by which the immune system detects host cells harboring the cysts to eliminate the latent stage of the parasite using mice with the H-2(d) haplotype, which are genetically resistant to the infection...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28446566/induction-of-adaptive-immunity-leads-to-nigrostriatal-disease-progression-in-mptp-mouse-model-of-parkinson-s-disease
#3
Goutam Chandra, Avik Roy, Suresh B Rangasamy, Kalipada Pahan
Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is the most widely used animal model for Parkinson's disease (PD), it is known that nigrostriatal pathologies do not persist in the acute MPTP mouse model. This study highlights the importance of adaptive immunity in driving persistent and progressive disease in acute MPTP-intoxicated mice. Although marked infiltration of T cells into the nigra was found on 1 d of MPTP insult, T cell infiltration decreased afterward, becoming normal on 30 d of insult...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28446565/murinization-and-h-chain-isotype-matching-of-the-anti-gitr-antibody-dta-1-reduces-immunogenicity-mediated-anaphylaxis-in-c57bl-6-mice
#4
Nicole A Belmar, Sarah W Chan, Melvin I Fox, Josue A Samayoa, Marcia M Stickler, Ninian N Tran, Yoshiko Akamatsu, Diane Hollenbaugh, Fiona A Harding, Hamsell M Alvarez
Recent advances in immuno-oncology have shown that the immune system can be activated to induce long-term, durable antitumor responses. For immuno-oncology drug development, immune activation is often explored using rat Abs in immunocompetent mouse models. Although these models can be used to show efficacy, antidrug immune responses to experimental protein-based therapeutics can arise. Immunogenicity of surrogate Abs may therefore represent an important obstacle to the evaluation of the antitumor efficacy of immunomodulator Abs in syngeneic models...
April 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28438900/definition-of-the-nature-and-hapten-threshold-of-the-%C3%AE-lactam-antigen-required-for-t-cell-activation-in-vitro-and-in-patients
#5
Xiaoli Meng, Zaid Al-Attar, Fiazia S Yaseen, Rosalind Jenkins, Caroline Earnshaw, Paul Whitaker, Daniel Peckham, Neil S French, Dean J Naisbitt, B Kevin Park
Covalent modification of protein by drugs may disrupt self-tolerance, leading to lymphocyte activation. Until now, determination of the threshold required for this process has not been possible. Therefore, we performed quantitative mass spectrometric analyses to define the epitopes formed in tolerant and hypersensitive patients taking the β-lactam antibiotic piperacillin and the threshold required for T cell activation. A hydrolyzed piperacillin hapten was detected on four lysine residues of human serum albumin (HSA) isolated from tolerant patients...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28438899/galectin-3-a-positive-regulator-of-leukocyte-recruitment-in-the-inflamed-microcirculation
#6
Beatrice R Gittens, Jennifer V Bodkin, Sussan Nourshargh, Mauro Perretti, Dianne Cooper
In vivo and ex vivo imaging were used to investigate the function of galectin-3 (Gal-3) during the process of leukocyte recruitment to the inflamed microcirculation. The cremasteric microcirculation of wild-type (C57BL/6), Gal-3(-/-), and CX3CR1(gfp/+) mice were assessed by intravital microscopy after PBS, IL-1β, TNF-α, or recombinant Gal-3 treatment. These cellular responses were investigated further using flow-chamber assays, confocal microscopy, flow cytometry, PCR analysis, and proteome array. We show that mechanisms mediating leukocyte slow rolling and emigration are impaired in Gal-3(-/-) mice, which could be because of impaired expression of cell adhesion molecules and an altered cell surface glycoproteome...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28438898/cytotoxic-t-cell-functions-accumulate-when-cd4-is-downregulated-by-cd4-t-cells-in-african-green-monkeys
#7
Carol L Vinton, Alexandra M Ortiz, Nina Calantone, Joseph C Mudd, Claire Deleage, David R Morcock, Sonya Whitted, Jacob D Estes, Vanessa M Hirsch, Jason M Brenchley
African green monkeys (AGMs) are a natural host of SIV that do not develop simian AIDS. Adult AGMs naturally have low numbers of CD4(+) T cells and a large population of MHC class II-restricted CD8αα T cells that are generated through CD4 downregulation in CD4(+) T cells. In this article, we study the functional profiles and SIV infection status in vivo of CD4(+) T cells, CD8αα T cells, and CD8αβ T cells in lymph nodes, peripheral blood, and bronchoalveolar lavage fluid of AGMs and rhesus macaques (in which CD4 downregulation is not observed)...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28438897/downregulation-of-mir-200a-3p-targeting-ctbp2-is-involved-in-the-hypoproduction-of-il-2-in-systemic-lupus-erythematosus-derived-t-cells
#8
Eri Katsuyama, Minglu Yan, Katsue Sunahori Watanabe, Syun Matsushima, Yuriko Yamamura, Sumie Hiramatsu, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Sonia Zeggar, Nobuya Yoshida, Vaishali R Moulton, George C Tsokos, Ken-Ei Sada, Jun Wada
Systemic lupus erythematosus (SLE) damages multiple organs by producing various autoantibodies. In this study, we report that decreased microRNA (miR)-200a-3p causes IL-2 hypoproduction through zinc finger E-box binding homeobox (ZEB)1 and C-terminal binding protein 2 (CtBP2) in a lupus-prone mouse. First, we performed RNA sequencing to identify candidate microRNAs and mRNAs involved in the pathogenesis of SLE. We found that miR-200a-3p was significantly downregulated, whereas its putative targets, ZEB2 and CtBP2, were upregulated in CD4(+) T cells from MRL/lpr-Tnfrsf6(lpr) mice compared with C57BL/6J mice...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28438896/mechanisms-that-shape-human-antibody-repertoire-development-in-mice-transgenic-for-human-ig-h-and-l-chain-loci
#9
Nancy S Longo, Tobias Rogosch, Michael Zemlin, Moncef Zouali, Peter E Lipsky
To determine the impact of the milieu on the development of the human B cell repertoire, we carried out a comprehensive analysis of productive and nonproductive Ig gene rearrangements from transgenic mice engineered to express single copies of the unrearranged human H chain and L chain Ig gene loci. By examining the nonproductive repertoire as an indication of the immediate product of the rearrangement machinery without an impact of selection, we discovered that the distribution of human rearrangements arising in the mouse was generally comparable to that seen in humans...
April 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28432147/cutting-edge-a-dual-tlr2-and-tlr7-ligand-induces-highly-potent-humoral-and-cell-mediated-immune-responses
#10
Alice Gutjahr, Laura Papagno, Francesco Nicoli, Alain Lamoureux, Fabienne Vernejoul, Thierry Lioux, Emma Gostick, David A Price, Gérard Tiraby, Eric Perouzel, Victor Appay, Bernard Verrier, Stéphane Paul
TLR agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. The aim of this study was to evaluate the immunostimulatory properties of a novel compound incorporating covalently linked moieties designed to stimulate both TLR2 and TLR7. This dual TLR2/TLR7 agonist induced the maturation of dendritic cells and primed substantial populations of cytolytic and highly polyfunctional effector CD8(+) T cells in vitro, and safely potentiated the immunogenic properties of a nanoparticulate Ag in vivo, eliciting humoral responses with a balanced TH1/TH2 profile in mice...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28432146/c1q-dependent-dendritic-cell-cross-presentation-of-in-vivo-formed-antigen-antibody-complexes
#11
Nataschja I Ho, Marcel G M Camps, Edwin F E de Haas, Leendert A Trouw, J Sjef Verbeek, Ferry Ossendorp
Dendritic cells (DCs) are specialized in Ag engulfment via a wide variety of uptake receptors on their cell surface. In the present study we investigated Ag uptake and presentation of in vivo-formed Ag-Ab complexes by i.v. injecting mice with Ag-specific Abs followed by the cognate Ag. We show by this natural Ab-mediated Ag targeting system that uptake by splenic APC subsets is severely hampered in mice lacking complement factor C1q (C1qa(-/-)). Moreover, no detectable Ag cross-presentation by CD8α(+) DCs from C1qa(-/-) mice was found...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28432145/bacterial-siderophores-hijack-neutrophil-functions
#12
Piu Saha, Beng San Yeoh, Rodrigo A Olvera, Xia Xiao, Vishal Singh, Deepika Awasthi, Bhagawat C Subramanian, Qiuyan Chen, Madhu Dikshit, Yanming Wang, Carole A Parent, Matam Vijay-Kumar
Neutrophils are the primary immune cells that respond to inflammation and combat microbial transgression. To thrive, the bacteria residing in their mammalian host have to withstand the antibactericidal responses of neutrophils. We report that enterobactin (Ent), a catecholate siderophore expressed by Escherichia coli, inhibited PMA-induced generation of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in mouse and human neutrophils. Ent also impaired the degranulation of primary granules and inhibited phagocytosis and bactericidal activity of neutrophils, without affecting their migration and chemotaxis...
April 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28424242/mtorc1-promotes-t-bet-phosphorylation-to-regulate-th1-differentiation
#13
Olesya Chornoguz, Robert S Hagan, Azeb Haile, Matthew L Arwood, Christopher J Gamper, Arnob Banerjee, Jonathan D Powell
CD4(+) T cells lacking the mTORC1 activator Rheb fail to secrete IFN-γ under Th1 polarizing conditions. We hypothesized that this phenotype is due to defects in regulation of the canonical Th1 transcription factor T-bet at the level of protein phosphorylation downstream of mTORC1. To test this hypothesis, we employed targeted mass-spectrometry proteomic analysis-multiple reaction monitoring mass spectrometry. We used this method to detect and quantify predicted phosphopeptides derived from T-bet. By analyzing activated murine wild-type and Rheb-deficient CD4(+) T cells, as well as murine CD4(+) T cells activated in the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to identify six T-bet phosphorylation sites...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28424241/microbiota-induced-antibodies-are-essential-for-host-inflammatory-responsiveness-to-sterile-and-infectious-stimuli
#14
Daniel Cisalpino, Caio T Fagundes, Camila B Brito, Fernando R Ascenção, Celso M Queiroz-Junior, Angélica T Vieira, Lirlândia P Sousa, Flávio A Amaral, Leda Q Vieira, Jacques R Nicoli, Mauro M Teixeira, Danielle G Souza
The indigenous intestinal microbiota is frequently considered an additional major organ of the human body and exerts profound immunomodulating activities. Germ-free (GF) mice display a significantly different inflammatory responsiveness pattern compared with conventional (CV) mice, and this was dubbed a "hyporesponsive phenotype." Taking into account that the deposition of immune complexes is a major event in acute inflammation and that GF mice have a distinct Ig repertoire and B cell activity, we aimed to evaluate whether this altered Ig repertoire interferes with the inflammatory responsiveness of GF mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28424240/the-histone-acetyltransferase-gcn5-positively-regulates-t-cell-activation
#15
Beixue Gao, Qingfei Kong, Yana Zhang, Chawon Yun, Sharon Y R Dent, Jianxun Song, Donna D Zhang, Yiming Wang, Xuemei Li, Deyu Fang
Histone acetyltransferases (HATs) regulate inducible transcription in multiple cellular processes and during inflammatory and immune response. However, the functions of general control nonrepressed-protein 5 (Gcn5), an evolutionarily conserved HAT from yeast to human, in immune regulation remain unappreciated. In this study, we conditionally deleted Gcn5 (encoded by the Kat2a gene) specifically in T lymphocytes by crossing floxed Gcn5 and Lck-Cre mice, and demonstrated that Gcn5 plays important roles in multiple stages of T cell functions including development, clonal expansion, and differentiation...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28424239/aim2-inflammasome-is-critical-for-influenza-induced-lung-injury-and-mortality
#16
Hongbo Zhang, Jiadi Luo, John F Alcorn, Kong Chen, Songqing Fan, Joseph Pilewski, Aizhong Liu, Wei Chen, Jay K Kolls, Jieru Wang
The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28424238/il-20-signaling-in-activated-human-neutrophils-inhibits-neutrophil-migration-and-function
#17
Portia Gough, Sundar Ganesan, Sandip K Datta
Neutrophils possess multiple antimicrobial mechanisms that are critical for protection of the host against infection with extracellular microbes, such as the bacterial pathogen Staphylococcus aureus Recruitment and activation of neutrophils at sites of infection are driven by cytokine and chemokine signals that directly target neutrophils via specific cell surface receptors. The IL-20 subfamily of cytokines has been reported to act at epithelial sites and contribute to psoriasis, wound healing, and anti-inflammatory effects during S...
April 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416603/high-throughput-immunogenetics-for-clinical-and-research-applications-in-immunohematology-potential-and-challenges
#18
Anton W Langerak, Monika Brüggemann, Frédéric Davi, Nikos Darzentas, Jacques J M van Dongen, David Gonzalez, Gianni Cazzaniga, Véronique Giudicelli, Marie-Paule Lefranc, Mathieu Giraud, Elizabeth A Macintyre, Michael Hummel, Christiane Pott, Patricia J T A Groenen, Kostas Stamatopoulos
Analysis and interpretation of Ig and TCR gene rearrangements in the conventional, low-throughput way have their limitations in terms of resolution, coverage, and biases. With the advent of high-throughput, next-generation sequencing (NGS) technologies, a deeper analysis of Ig and/or TCR (IG/TR) gene rearrangements is now within reach, which impacts on all main applications of IG/TR immunogenetic analysis. To bridge the generation gap from low- to high-throughput analysis, the EuroClonality-NGS Consortium has been formed, with the main objectives to develop, standardize, and validate the entire workflow of IG/TR NGS assays for 1) clonality assessment, 2) minimal residual disease detection, and 3) repertoire analysis...
April 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416602/antigen-receptor-galaxy-a-user-friendly-web-based-tool-for-analysis-and-visualization-of-t-and-b-cell-receptor-repertoire-data
#19
Hanna IJspeert, Pauline A van Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Andrew P Stubbs, Mirjam van der Burg
Antigen Receptor Galaxy (ARGalaxy) is a Web-based tool for analyses and visualization of TCR and BCR sequencing data of 13 species. ARGalaxy consists of four parts: the demultiplex tool, the international ImMunoGeneTics information system (IMGT) concatenate tool, the immune repertoire pipeline, and the somatic hypermutation (SHM) and class switch recombination (CSR) pipeline. Together they allow the analysis of all different aspects of the immune repertoire. All pipelines can be run independently or combined, depending on the available data and the question of interest...
April 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28416601/csreport-a-new-computational-tool-designed-for-automatic-analysis-of-class-switch-recombination-junctions-sequenced-by-high-throughput-sequencing
#20
François Boyer, Hend Boutouil, Iman Dalloul, Zeinab Dalloul, Jeanne Cook-Moreau, Jean-Claude Aldigier, Claire Carrion, Bastien Herve, Erwan Scaon, Michel Cogné, Sophie Péron
B cells ensure humoral immune responses due to the production of Ag-specific memory B cells and Ab-secreting plasma cells. In secondary lymphoid organs, Ag-driven B cell activation induces terminal maturation and Ig isotype class switch (class switch recombination [CSR]). CSR creates a virtually unique IgH locus in every B cell clone by intrachromosomal recombination between two switch (S) regions upstream of each C region gene. Amount and structural features of CSR junctions reveal valuable information about the CSR mechanism, and analysis of CSR junctions is useful in basic and clinical research studies of B cell functions...
April 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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