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Helios T cell

M Daves, J Blecken, T Matthias, A Frey, V Perkmann, A Dall Acqua, A Joos, S Platzgummer
The IIF using the HEp-2 cell substrate should be still considered the "gold standard" techniques for determination of antinuclear antibody (ANA). Standardization and automation can be considered to be still in progress. Aim of this study was to evaluate the performance of the commercially automated indirect immunofluorescent antinuclear HEp-2 antibody assay. The study was designed to compare two commercially available HEp-2 ANA by indirect immunofluorescent antibody assays using a sensitivity panel (120 clinically determined patients) and a specificity panel consisting of 78 clinically confirmed negative patients...
October 14, 2016: Immunologic Research
Shaorong Zhao, Wei Liu, Yinghui Li, Pengjiang Liu, Shufang Li, Daolei Dou, Yue Wang, Rongcun Yang, Rong Xiang, Feifei Liu
The molecular defects which lead to multistep incidences of human T-cell leukemia have yet to be identified. The DNA-binding protein Helios (known as IKZF2), a member of the Ikaros family of Krüppel-like zinc-finger proteins, functions pivotally in T-cell differentiation and activation. In this study, we identify three novel short Helios splice variants which are T-cell leukemic specific, and demonstrate their dominant-negative function. We then test the cellular localization of distinct Helios isoforms, as well as their capability to form heterodimer with Ikaros, and the association with complexes comprising histone deacetylase (HDAC)...
2016: PloS One
Michael J Haller, Stephen E Gitelman, Peter A Gottlieb, Aaron W Michels, Daniel J Perry, Andrew R Schultz, Maigan A Hulme, Jonathan J Shuster, Baiming Zou, Clive H Wasserfall, Amanda Posgai, Clayton E Mathews, Todd M Brusko, Mark A Atkinson, Desmond A Schatz
Low-dose anti-thymocyte globulin (ATG) + pegylated granulocyte-colony stimulating factor (G-CSF) preserves beta cell function for at least 12-months in type 1 diabetes (T1D). Herein, we describe metabolic and immunologic parameters 24-months following treatment. Patients with established T1D (duration 4-24 months) were randomized to ATG and peg-G-CSF (N=17) or placebo (N=8). Primary outcomes included AUC C-peptide following mixed-meal tolerance test (MMTT) and flow cytometry. "Responders" (12-month C-peptide ≥ baseline), "Super-responders" (24-month C-peptide ≥ baseline), and "Non-responders" (12-month C-peptide < baseline) were evaluated for biomarkers of outcome...
September 26, 2016: Diabetes
Christian H Gabriel, Fridolin Gross, Martin Karl, Heike Stephanowitz, Anna Floriane Hennig, Melanie Weber, Stefanie Gryzik, Ivo Bachmann, Katharina Hecklau, Jürgen Wienands, Johannes Schuchhardt, Hanspeter Herzel, Andreas Radbruch, Eberhard Krause, Ria Baumgrass
Transcription factors of the nuclear factor of activated T cell (NFAT)-family are essential for antigen-specific T cell activation and differentiation. Their cooperative DNA binding with other transcription factors, such as AP1-proteins (FOS, JUN, JUNB), FOXP3, IRFs and EGR1, dictate the gene regulatory action of NFATs. To identify as yet unknown interaction partners of NFAT, we purified biotin tagged NFATc1/αA, NFATc1/βC and NFATc2/C protein-complexes and analyzed their components by SILAC-based mass spectrometry...
September 16, 2016: Journal of Biological Chemistry
Eleonora Timperi, Ilenia Pacella, Valeria Schinzari, Chiara Focaccetti, Luca Sacco, Francesco Farelli, Roberto Caronna, Gabriella Del Bene, Flavia Longo, Antonio Ciardi, Sergio Morelli, Anna Rita Vestri, Piero Chirletti, Vincenzo Barnaba, Silvia Piconese
Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor...
July 2016: Oncoimmunology
Neha Jariwala, Bernice Benoit, Andrew V Kossenkov, Landon K Oetjen, Timothy M Whelan, Christine M Cornejo, Junko Takeshita, Brian S Kim, Louise C Showe, Maria Wysocka, Alain H Rook
No abstract text is available yet for this article.
September 1, 2016: Journal of Investigative Dermatology
Duke Geem, Vu Ngo, Akihito Harusato, Benoit Chassaing, Andrew T Gewirtz, Rodney D Newberry, Timothy L Denning
: This study showed that the absence of CCR7 or mesenteric lymph nodes/gut-associated lymphoid tissue did not appreciably impact total intestinal Foxp3+ regulatory T cell representation in the steady-state. However, mesenteric lymph nodes/GALT are required for normal peripherally induced Foxp3+ regulatory T cell differentiation in the small intestine, but not in the large intestine. BACKGROUND & AIMS: Foxp3+ regulatory T cells (Tregs) in the intestine promote immune tolerance to enteric antigens...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
Zuzana Parackova, Jana Kayserova, Klara Danova, Kristyna Sismova, Eva Dudkova, Zdenek Sumnik, Stanislava Kolouskova, Jan Lebl, Katerina Stechova, Anna Sediva
T regulatory cells (Tregs) are essential for maintaining tolerance and preventing autoimmune diseases, such as type 1 diabetes (T1D). In our study, we investigated CD25 + FoxP3 + Tregs and thymic FoxP3 + Helios + Tregs in large cohorts of children with T1D at onset and with long-term T1D, and further in their relatives and healthy controls. We observed significantly decreased numbers of CD25 + FoxP3 + Tregs, but not FoxP3 + Helios + Tregs, in long-term patients compared with the control group and T1D onset...
August 25, 2016: Autoimmunity
Chen Liu, Zhao Guan, Lei Zhao, Ying Song, Hui Wang
OBJECTIVE: This study was designed to investigate the expression of regulatory T cells in primary Sjögren's Syndrome (pSS) and to evaluate the clinical role of CD4(+)Helios(+)FoxP3(+) cells in pSS patients. METHODS: CD4(+)FoxP3(+) T cells in the peripheral blood of 39 pSS patients and 30 healthy controls were measured by flow cytometry and CD25 and Helios expression were also analyzed. The repression ability of CD4(+)CD25(hi) cells was tested in vitro. Clinical information of pSS patients was retrospectively collected and their correlations with circulating Treg cells were analyzed...
August 19, 2016: Modern Rheumatology
Julie L Mitchell, Amara Seng, Thomas M Yankee
The Ikaros family of transcription factors is essential for normal T cell development, but their expression pattern in human thymocytes remains poorly defined. Our goal is to determine how protein levels of Ikaros, Helios, and Aiolos change as human thymocytes progress through the positive selection and lineage commitment stages. To accomplish this goal, we used multi-parameter flow cytometry to define the populations in which positive selection and lineage commitment are most likely to occur. After human thymocytes express CD3 and receive positive selection signals, the cells down-regulate expression of CD4 to become transitional single positive (TSP) CD8(+) thymocytes...
August 9, 2016: Immunology
Anthony Atala
No abstract text is available yet for this article.
August 2016: Journal of Urology
Guilherme Muniz Bourroul, Hélio José Fragoso, José Walter Feitosa Gomes, Vivian Sati Oba Bourroul, Celina Tizuko Fujiyama Oshima, Thiago Simão Gomes, Gabriela Tognini Saba, Rogério Tadeu Palma, Jaques Waisberg
OBJECTIVE: To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. METHODS: Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues...
April 2016: Einstein
Gelena V Lifshitz, Dmitry D Zhdanov, Anastasia V Lokhonina, Daria D Eliseeva, Elena Y Lyssuck, Igor A Zavalishin, Svetlana N Bykovskaia
Multiple sclerosis (MS) is an autoimmune disease characterized by defect in regulatory function of CD4(+)CD25(+) T cells. We demonstrated difference in proportion of regulatory T cells CD4(+)CD25(+)FoxP3(+)CD127(low) (Tregs) within the same patients' relapse and remission. Proportion of peripheral Tregs (pTregs) dropped almost two times in the relapse compare to remission. Levels of pTregs in patients' remission were lower than in healthy donors. Suppressive ability of pTregs was decreased in MS patients compared to healthy donors...
July 16, 2016: Autoimmunity
Jincao Tang, Renjie Yang, Ling Lv, Aihua Yao, Liyong Pu, Aihong Yin, Xiangcheng Li, Yue Yu, Scott L Nyberg, Xuehao Wang
Acute rejection is commonly encountered for long-term survival in liver transplant (LT) recipients and may impact their long-term survival if rejection is severe or recurrent. The aim of this study is to examine the therapeutic potential of transforming growth factor (TGF-β)-overexpressing mesenchymal stem cells (MSCs) in inducing a local immunosuppression in liver grafts after transplantation. MSCs were transduced with a lentiviral vector expressing the human TGF-β1 gene; TGF-β1-overexpressing MSCs (designated as TGF/MSCs) were then transfused into the liver grafts via the portal vein of a rat LT model of acute rejection...
June 22, 2016: Stem Cells
Mostafa G Aly, Karina Trojan, Rolf Weimer, Christian Morath, Gerhard Opelz, Mohammed A Tohamy, Volker Daniel
BACKGROUND: Regulatory T cells (Tregs) are a cornerstone of graft acceptance. High numbers of Tregs are associated with better long-term graft survival. Recently, Vitamin D was suggested as an immunomodulator, in addition to its classical role in calcium metabolism. Vitamin D modulates Tregs and might, thereby, promote graft acceptance and long-term graft survival. METHODS: One hundred twenty-three renal allograft recipients attending either Heidelberg nephrology or Giessen internal medicine clinic were enrolled in this cross- sectional study...
2016: BMC Pharmacology & Toxicology
Vinicius Rosa, Han Xie, Nileshkumar Dubey, Thulasi T Madanagopal, Sneha S Rajan, Julien Luc Paul Morin, Intekhab Islam, Antônio Hélio Castro Neto
OBJECTIVE: The aim of this study was to evaluate the cytotoxicity and differentiation potential of a graphene oxide (GO)-based substrate using dental pulp stem cell (DPSC). METHODS: GO was obtained via chemical exfoliation of graphite using the modified Hummer's method and dispersed in water-methanol solution. 250μL of 1.5mg/mL solution were added to a cover slip and allowed to dry (25°C, 24h). GO-based substrate was characterized by Raman spectroscopy, AFM and contact angle...
August 2016: Dental Materials: Official Publication of the Academy of Dental Materials
Xuehui He, Sija Landman, Stijn C G Bauland, Juliette van den Dolder, Hans J P M Koenen, Irma Joosten
Regulatory T cells (Treg) are important for immune homeostasis and are considered of great interest for immunotherapy. The paucity of Treg numbers requires the need for ex vivo expansion. Although therapeutic Treg flow-sorting is feasible, most centers aiming at Treg-based therapy focus on magnetic bead isolation of CD4+CD25+ Treg using a good manufacturing practice compliant closed system that achieves lower levels of cell purity. Polyclonal Treg expansion protocols commonly use anti-CD3 plus anti-CD28 monoclonal antibody (mAb) stimulation in the presence of rhIL-2, with or without rapamycin...
2016: PloS One
Laurent Beziaud, Laura Mansi, Patrice Ravel, Elodie Lauret Marie-Joseph, Caroline Laheurte, Laurie Rangan, Francis Bonnefoy, Jean-René Pallandre, Laura Boullerot, Clémentine Gamonet, Sindy Vrecko, Lise Queiroz, Tristan Maurina, Guillaume Mouillet, Thierry Nguyen Tan Hon, Elsa Curtit, Bernard Royer, Béatrice Gaugler, Jagadeesh Bayry, Eric Tartour, Antoine Thiery-Vuillemin, Xavier Pivot, Christophe Borg, Yann Godet, Olivier Adotévi
The rapalogs everolimus and temsirolimus that inhibit mTOR signaling are used as antiproliferative drugs in several cancers. Here we investigated the influence of rapalogs-mediated immune modulation on their antitumor efficacy. Studies in metastatic renal cell carcinoma patients showed that everolimus promoted high expansion of FoxP3 (+)Helios(+)Ki67(+) regulatory CD4 T cells (Tregs). In these patients, rapalogs strongly enhanced the suppressive functions of Tregs, mainly in a contact-dependent manner. Paradoxically, a concurrent activation of spontaneous tumor-specific Th1 immunity also occurred...
July 15, 2016: Cancer Research
Hidetoshi Nakagawa, Jessica M Sido, Edwin E Reyes, Valerie Kiers, Harvey Cantor, Hye-Jung Kim
Expression of the transcription factor Helios by Tregs ensures stable expression of a suppressive and anergic phenotype in the face of intense inflammatory responses, whereas Helios-deficient Tregs display diminished lineage stability, reduced FoxP3 expression, and production of proinflammatory cytokines. Here we report that selective Helios deficiency within CD4 Tregs leads to enhanced antitumor immunity through induction of an unstable phenotype and conversion of intratumoral Tregs into T effector cells within the tumor microenvironment...
May 31, 2016: Proceedings of the National Academy of Sciences of the United States of America
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