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81.
Butler MO Imataki O Yamashita Y Tanaka M Ansén S Berezovskaya A Metzler G Milstein MI Mooney MM Murray AP Mano H Nadler LM Hirano N 《PloS one》2012,7(1):e30229
Background
Using in vivo mouse models, the mechanisms of CD4+ T cell help have been intensively investigated. However, a mechanistic analysis of human CD4+ T cell help is largely lacking. Our goal was to elucidate the mechanisms of human CD4+ T cell help of CD8+ T cell proliferation using a novel in vitro model.Methods/Principal Findings
We developed a genetically engineered novel human cell-based artificial APC, aAPC/mOKT3, which expresses a membranous form of the anti-CD3 monoclonal antibody OKT3 as well as other immune accessory molecules. Without requiring the addition of allogeneic feeder cells, aAPC/mOKT3 enabled the expansion of both peripheral and tumor-infiltrating T cells, regardless of HLA-restriction. Stimulation with aAPC/mOKT3 did not expand Foxp3+ regulatory T cells, and expanded tumor infiltrating lymphocytes predominantly secreted Th1-type cytokines, interferon-γ and IL-2. In this aAPC-based system, the presence of autologous CD4+ T cells was associated with significantly improved CD8+ T cell expansion in vitro. The CD4+ T cell derived cytokines IL-2 and IL-21 were necessary but not sufficient for this effect. However, CD4+ T cell help of CD8+ T cell proliferation was partially recapitulated by both adding IL-2/IL-21 and by upregulation of IL-21 receptor on CD8+ T cells.Conclusions
We have developed an in vitro model that advances our understanding of the immunobiology of human CD4+ T cell help of CD8+ T cells. Our data suggests that human CD4+ T cell help can be leveraged to expand CD8+ T cells in vitro. 相似文献82.
David A. Mead Susan Lucas Alex Copeland Alla Lapidus Jan-Feng Cheng David C. Bruce Lynne A. Goodwin Sam Pitluck Olga Chertkov Xiaojing Zhang John C. Detter Cliff S. Han Roxanne Tapia Miriam Land Loren J. Hauser Yun-juan Chang Nikos C. Kyrpides Natalia N. Ivanova Galina Ovchinnikova Tanja Woyke Catherine Brumm Rebecca Hochstein Thomas Schoenfeld Phillip Brumm 《Standards in genomic sciences》2012,6(3):381-400
83.
I Anderson E Saunders A Lapidus M Nolan S Lucas H Tice TG Del Rio JF Cheng C Han R Tapia LA Goodwin S Pitluck K Liolios K Mavromatis I Pagani N Ivanova N Mikhailova A Pati A Chen K Palaniappan M Land L Hauser CD Jeffries YJ Chang EM Brambilla M Rohde S Spring M Göker JC Detter T Woyke J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk 《Standards in genomic sciences》2012,6(2):155-164
Thermodesulfatator indicus Moussard et al. 2004 is a member of the Thermodesulfobacteriaceae, a family in the phylum Thermodesulfobacteria that is currently poorly characterized at the genome level. Members of this phylum are of interest because they represent a distinct, deep-branching, Gram-negative lineage. T. indicus is an anaerobic, thermophilic, chemolithoautotrophic sulfate reducer isolated from a deep-sea hydrothermal vent. Here we describe the features of this organism, together with the complete genome sequence, and annotation. The 2,322,224 bp long chromosome with its 2,233 protein-coding and 58 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
84.
A Copeland A Zeytun M Yassawong M Nolan S Lucas N Hammon S Deshpande JF Cheng C Han R Tapia LA Goodwin S Pitluck K Mavromatis K Liolios I Pagani N Ivanova N Mikhailova A Pati A Chen K Palaniappan M Land L Hauser CD Jeffries EM Brambilla M Rohde J Sikorski R Pukall M Göker JC Detter T Woyke J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk A Lapidus 《Standards in genomic sciences》2012,6(2):240-250
Deinococcus proteolyticus (ex Kobatake et al. 1973) Brook and Murray 1981 is one of currently 47 species in the genus Deinococcus within the family Deinococcaceae. Strain MRP(T) was isolated from feces of Lama glama and possesses extreme radiation resistance, a trait is shares with various other species of the genus Deinococcus, with D. proteolyticus being resistant up to 1.5 Mrad of gamma radiation. Strain MRP(T) is of further interest for its carotenoid pigment. The genome presented here is only the fifth completed genome sequence of a member of the genus Deinococcus (and the forth type strain) to be published, and will hopefully contribute to a better understanding of how members of this genus adapted to high gamma- or UV ionizing-radiation. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,886,836 bp long genome with its four large plasmids of lengths 97 kbp, 132 kbp, 196 kbp and 315 kbp harbors 2,741 protein-coding and 58 RNA genes and is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
85.
B Abt C Han C Scheuner M Lu A Lapidus M Nolan S Lucas N Hammon S Deshpande JF Cheng R Tapia LA Goodwin S Pitluck K Liolios I Pagani N Ivanova K Mavromatis N Mikhailova M Huntemann A Pati A Chen K Palaniappan M Land L Hauser EM Brambilla M Rohde S Spring S Gronow M Göker T Woyke J Bristow JA Eisen V Markowitz P Hugenholtz NC Kyrpides HP Klenk JC Detter 《Standards in genomic sciences》2012,6(2):194-209
Spirochaeta coccoides Dröge et al. 2006 is a member of the genus Spirochaeta Ehrenberg 1835, one of the oldest named genera within the Bacteria. S. coccoides is an obligately anaerobic, Gram-negative, non-motile, spherical bacterium that was isolated from the hindgut contents of the termite Neotermes castaneus. The species is of interest because it may play an important role in the digestion of breakdown products from cellulose and hemicellulose in the termite gut. Here we provide a taxonomic re-evaluation for strain SPN1T, and based on physiological and genomic characteristics, we propose its reclassification as a novel species in the genus Sphaerochaeta, a recently published sister group of the Spirochaeta. The 2,227,296 bp long genome of strain SPN1T with its 1,866 protein-coding and 58 RNA genes is a part of the Genomic
Encyclopedia of
Bacteria and
Archaea project. 相似文献
86.
87.
88.
Vijay Alla Bhavani S. Kowtharapu David Engelmann Stephan Emmrich Ulf Schmitz Marc Steder Brigitte M. Pützer 《Cell cycle (Georgetown, Tex.)》2012,11(16):3067-3078
Resistance to anti-neoplastic agents is the major cause of therapy failure, leading to disease recurrence and metastasis. E2F1 is a strong inducer of apoptosis in response to DNA damage through its capacity to activate p53/p73 death pathways. Recent evidence, however, showed that E2F1, which is aberrantly expressed in advanced malignant melanomas together with antagonistic p73 family members, drives cancer progression. Investigating mechanisms responsible for dysregulated E2F1 losing its apoptotic function, we searched for genomic signatures in primary and late clinical tumor stages to allow the prediction of downstream effectors associated with apoptosis resistance and survival of aggressive melanoma cells. We identified miR-205 as specific target of p73 and found that upon genotoxic stress, its expression is sufficiently abrogated by endogenous DNp73. Significantly, metastatic cells can be rescued from drug resistance by selective knockdown of DNp73 or overexpression of miR-205 in p73-depleted cells, leading to increased apoptosis and the reduction of tumor growth in vivo. Our data delineate an autoregulatory circuit, involving high levels of E2F1 and DNp73 to downregulate miR-205, which, in turn, controls E2F1 accumulation. Finally, drug resistance associated to this genetic signature is mediated by removing the inhibitory effect of miR-205 on the expression of Bcl-2 and the ATP-binding cassette transporters A2 (ABCA2) and A5 (ABCA5) related to multi-drug resistance and malignant progression. These results define the E2F1-p73/DNp73-miR-205 axis as a crucial mechanism for chemoresistance and, thus, as a target for metastasis prevention. 相似文献
89.
CheY, the excitatory response regulator in the chemotaxis system of Escherichia coli, can be modulated by two covalent modifications: phosphorylation and acetylation. Both modifications have been detected in vitro only. The role of CheY acetylation is still obscure, although it is known to be involved in chemotaxis and to occur in vitro by two mechanisms—acetyl-CoA synthetase-catalyzed transfer of acetyl groups from acetate to CheY and autocatalyzed transfer from AcCoA. Here, we succeeded in detecting CheY acetylation in vivo by three means—Western blotting with a specific anti-acetyl-lysine antibody, mass spectrometry, and radiolabeling with [14C]acetate in the presence of protein-synthesis inhibitor. Unexpectedly, the level and rate of CheY acetylation in vivo were much higher than that in vitro. Thus, before any treatment, 9-13% of the lysine residues were found acetylated, depending on the growth phase, meaning that, on average, essentially every CheY molecule was acetylated in vivo. This high level was mainly the outcome of autoacetylation. Addition of acetate caused an incremental increase in the acetylation level, in which acetyl-CoA synthetase was involved too. These findings may have far-reaching implications for the structure-function relationship of CheY. 相似文献
90.
Intrinsically disordered proteins (IDPs) lack a well-defined three-dimensional structure under physiological conditions. Intrinsic disorder is a common phenomenon, particularly in multicellular eukaryotes, and is responsible for important protein functions including regulation and signaling. Many disease-related proteins are likely to be intrinsically disordered or to have disordered regions. In this paper, a new predictor model based on the Bayesian classification methodology is introduced to predict for a given protein or protein region if it is intrinsically disordered or ordered using only its primary sequence. The method allows to incorporate length-dependent amino acid compositional differences of disordered regions by including separate statistical representations for short, middle and long disordered regions. The predictor was trained on the constructed data set of protein regions with known structural properties. In a Jack-knife test, the predictor achieved the sensitivity of 89.2% for disordered and 81.4% for ordered regions. Our method outperformed several reported predictors when evaluated on the previously published data set of Prilusky et al. [2005. FoldIndex: a simple tool to predict whether a given protein sequence is intrinsically unfolded. Bioinformatics 21 (16), 3435-3438]. Further strength of our approach is the ease of implementation. 相似文献