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double negative T cell

Sara De Biasi, Elena Bianchini, Milena Nasi, Margherita Digaetano, Lara Gibellini, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Marcello Pinti, Cristina Mussini, Andrea Cossarizza
INTRODUCTION: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients. METHODS: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR)...
November 13, 2016: AIDS
Mansoureh Tajaddod, Andrea Tanzer, Konstantin Licht, Michael T Wolfinger, Stefan Badelt, Florian Huber, Oliver Pusch, Sandy Schopoff, Michael Janisiw, Ivo Hofacker, Michael F Jantsch
BACKGROUND: Short interspersed elements (SINEs) represent the most abundant group of non-long-terminal repeat transposable elements in mammalian genomes. In primates, Alu elements are the most prominent and homogenous representatives of SINEs. Due to their frequent insertion within or close to coding regions, SINEs have been suggested to play a crucial role during genome evolution. Moreover, Alu elements within mRNAs have also been reported to control gene expression at different levels...
October 25, 2016: Genome Biology
Andreas Keil, Sean R Hall, Meike Körner, Martin Herrmann, Ralph A Schmid, Steffen Frese
BACKGROUND: Since the precise mechanism for the pathogenesis of systemic lupus erythematosus (SLE) is unknown, no targeted therapies in addition to immunosuppression are available so far. We recently demonstrated that administration of the topoisomerase I (topo I) inhibitor irinotecan at extremely low concentrations reversed established lupus nephritis in NZB/NZW mice. While profound immunosuppression was absent, we proposed changes in DNA relaxation and anti-double-stranded (ds)DNA antibody binding as the underlying mechanism...
October 22, 2016: Arthritis Research & Therapy
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
October 17, 2016: Immunobiology
Guoping Fu, Mei Yu, Yuhong Chen, Yongwei Zheng, Wen Zhu, Debra K Newman, Demin Wang, Renren Wen
Pre-T cell receptor (TCR) signaling is required for pre-T cell survival, proliferation, and differentiation from the CD4 and CD8 double negative (DN) to the double positive (DP) stage. However, the pre-TCR signal transduction pathway is not fully understood and the signaling molecules involved have not been completely identified. Phospholipase Cγ (PLCγ) 1 is an important signaling molecule that generates two second messengers, diacylglycerol and inositol 1,4,5-trisphosphate, that are important to mediate PKC activation and intracellular Ca(2+) flux in many signaling pathways...
October 19, 2016: European Journal of Immunology
Neta Goldschmidt, Fares Darawshy, Geffen Kleinstern, Elena Slyusarevsky, Galina Pogrebijski, Svetlana Krichevsky, Dina Ben-Yehuda, Moshe E Gatt
We retrospectively studied the prognostic role of molecular (gene rearrangement, GRR) bone marrow (BM) involvement in diffuse large B-cell lymphoma (DLBCL, 424 patients) and in peripheral T-cell lymphoma (PTCL, 67 patients). When correlating BM GRR to histological findings at diagnosis, the GRR test was more sensitive (p = 0.036) but less specific (p < 0.0001) in PTCL than in DLBCL. For DLBCL (but not PTCL), a positive BM GRR correlated with advanced stage (p = 0.0001) and high IPI (p = 0...
October 18, 2016: Leukemia & Lymphoma
Zhen Wang, Fuxing Wang, Yechun Hong, Jirong Huang, Huazhong Shi, Jian-Kang Zhu
Chloroplast as the site for photosynthesis is an essential organelle in plants, but little is known about its role in stomatal regulation and drought resistance. In this study, we show that two chloroplastic proteins essential for thylakoid formation negatively regulate drought resistance in Arabidopsis. By screening a mutant pool with T-DNA insertions in nuclear genes encoding chloroplastic proteins, we identified a HCF106 knockdown mutant exhibiting increased resistance to drought stress. The hcf106 mutant displayed elevated levels of reactive oxygen species (ROS) in guard cells, improved stomatal closure and reduced water loss under drought conditions...
October 15, 2016: Plant Physiology
Dibyendu Kumar Das, Robert J Mallis, Jonathan S Duke-Cohan, Rebecca E Hussey, Paul W Tetteh, Mark Hilton, Gerhard Wagner, Matthew J Lang, Ellis Reinherz
The pre-T cell receptor (preTCR) is a pTα-β heterodimer functioning in early αβ T-cell development. Although once thought to be ligand-autonomous, recent studies show that preTCRs participate in thymic repertoire formation through recognition of peptides bound to major histocompatibility molecules (pMHC). Using optical tweezers, we probe preTCR bonding with pMHC at the single molecule level. Like the αβTCR, the preTCR is a mechanosensor undergoing force-based structural transitions that dynamically enhance bond lifetimes, and exploiting allosteric control regulated via the Cβ FG loop region...
October 5, 2016: Journal of Biological Chemistry
F Belva, M Bonduelle, M Roelants, D Michielsen, A Van Steirteghem, G Verheyen, H Tournaye
STUDY QUESTION: What is the semen quality of young adult men who were conceived 18-22 years ago by ICSI for male infertility? SUMMARY ANSWER: In this cohort of 54 young adult ICSI men, median sperm concentration, total sperm count and total motile sperm count were significantly lower than in spontaneously conceived peers. WHAT IS KNOWN ALREADY: The oldest ICSI offspring cohort worldwide has recently reached adulthood. Hence, their reproductive health can now be investigated...
October 5, 2016: Human Reproduction
Isabelle Mothe-Satney, Joseph Murdaca, Brigitte Sibille, Anne-Sophie Rousseau, Raphaëlle Squillace, Gwenaëlle Le Menn, Akila Rekima, Frederic Larbret, Juline Pelé, Valérie Verhasselt, Paul A Grimaldi, Jaap G Neels
Metabolism plays an important role in T cell biology and changes in metabolism drive T cell differentiation and fate. Most research on the role of metabolism in T lymphocytes focuses on mature T cells while only few studies have investigated the role of metabolism in T cell development. In this study, we report that activation or overexpression of the transcription factor Peroxisome Proliferator-Activated Receptor β (PPARβ) increases fatty acid oxidation in T cells. Furthermore, using both in vivo and in vitro models, we demonstrate that PPARβ activation/overexpression inhibits thymic T cell development by decreasing proliferation of CD4(-)CD8(-) double-negative stage 4 (DN4) thymocytes...
September 29, 2016: Scientific Reports
Sara De Biasi, Elena Bianchini, Milena Nasi, Margherita Digaetano, Lara Gibellini, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Marcello Pinti, Cristina Mussini, Andrea Cossarizza
INTRODUCTION: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV+ patients (pts). METHODS: By flow cytometry, we studied iNKT cells from 54 HIV+ pts who started combined antiretroviral therapy (cART) and had undetectable viral load for >1 year. Twenty-five maintained a CD4/CD8 ratio <0.4, while 29 reached a ratio >1.1; 32 age- and sex-matched subjects were healthy controls (CTR). RESULTS: Pts with low ratio had lower percentage of CD4+ iNKT cells compared to pts with high ratio, and higher CD8+ iNKT cell percentage; double negative (DN) iNKT cells were lower in HIV+ pts compared to CTR...
September 24, 2016: AIDS
Yalei Liu, Ran You, Nan Yu, Yan Gong, Chenxue Qu, Yang Zhang, Guizhi Lu, Youyuan Huang, Hong Zhang, Ying Gao, Yanming Gao, Xiaohui Guo
Both cellular and humoral responses play important roles in the pathogenesis of Hashimoto's thyroiditis (HT). However, the immunological differences between euthyroid (mild HT) and hypothyroid (severe HT) patients are unknown. This study aimed to investigate the distribution of lymphocyte subsets and cytokine profiles in HT patients with differences in thyroid function. Peripheral blood was drawn from 18 healthy controls and 54 HT patients (33 patients with mild HT, 21 patients with severe HT). The percentages of B cell subsets, T cell subsets and NK cells were analyzed by flow cytometry...
September 23, 2016: International Immunopharmacology
M Evans, T Murofushi, H Tsuda, Y Mikami, N Zhao, K Ochiai, T Kurita-Ochiai, M Yamamoto, K Otsuka, N Suzuki
BACKGROUND AND OBJECTIVE: Bacteria in the dental biofilm surrounding marginal gingival grooves cause periodontal diseases. Numerous bacteria within the biofilm consume nutrients from the gingival crevicular fluid. Furthermore, some gram-negative bacteria in mature dental biofilms produce butyrate. Thus, gingival epithelial cells in close proximity to mature dental biofilms are at risk of both starvation and exposure to butyrate. In the present study, we determined the combined effects of starvation and butyrate exposure on gingival epithelial cell death and the underlying mechanisms...
September 13, 2016: Journal of Periodontal Research
Hideyuki Ishiguro, Takehiro Wakasugi, Yukio Terashita, Nobuhiro Sakamoto, Tatsuya Tanaka, Koji Mizoguchi, Hiroyuki Sagawa, Tomotaka Okubo, Hiromitsu Takeyama
BACKGROUND: E-cadherin/CDH1 is one of the proteins involved in cell adhesion, and it is known that decreased expression of E-cadherin induces lymph node metastasis in esophageal cancer. Beta catenin/CTNNB1, which is an important component of the Wnt signaling pathway, binds to E-cadherin at the cell membrane, where the complex of these two proteins functions in the stabilization of cell adhesion. However, its role in the pathogenesis of esophageal cancer is still unknown. METHODS: This study included 86 patients with esophageal cancer who underwent surgery between 1998 and 2007...
2016: World Journal of Surgical Oncology
Alistair L Chenery, Frann Antignano, Michael R Hughes, Kyle Burrows, Kelly M McNagny, Colby Zaph
Pro-inflammatory cytokines produced during immune responses to infectious stimuli are well-characterized to have secondary effects on the function of hematopoietic progenitor cells in the bone marrow (BM). However, these effects on the BM are poorly characterized during chronic infection with intestinal helminth parasites. In this study, we use the Trichuris muris model of infection and show that Th1 cell-associated, but not acute Th2 cell-associated, responses to chronic T. muris infection cause a major, transient expansion of CD48(-) CD150(-) multipotent progenitor cells in the BM that is dependent on the presence of adaptive immune cells and IFN-γ signalling...
September 4, 2016: European Journal of Immunology
Russell Silowash, Liron Pantanowitz, Fiona E Craig, Jeffrey P Simons, Sara E Monaco
BACKGROUND: Fine-needle aspiration (FNA) coupled with flow cytometry (FC) can be helpful in suspicious pediatric lymph nodes or masses to exclude a lymphoproliferative disorder. The aim of this study was to analyze FC findings in a series of pediatric FNAs and to correlate abnormal findings with follow-up information. MATERIALS AND METHODS: All pediatric FNAs performed at a tertiary-care children's hospital over a 46-month period that had FC performed were retrospectively analyzed and correlated with follow-up...
2016: Acta Cytologica
Nicole Vincent Jordan, Aditya Bardia, Ben S Wittner, Cyril Benes, Matteo Ligorio, Yu Zheng, Min Yu, Tilak K Sundaresan, Joseph A Licausi, Rushil Desai, Ryan M O'Keefe, Richard Y Ebright, Myriam Boukhali, Srinjoy Sil, Maristela L Onozato, Anthony J Iafrate, Ravi Kapur, Dennis Sgroi, David T Ting, Mehmet Toner, Sridhar Ramaswamy, Wilhelm Haas, Shyamala Maheswaran, Daniel A Haber
Circulating tumour cells in women with advanced oestrogen-receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer acquire a HER2-positive subpopulation after multiple courses of therapy. In contrast to HER2-amplified primary breast cancer, which is highly sensitive to HER2-targeted therapy, the clinical significance of acquired HER2 heterogeneity during the evolution of metastatic breast cancer is unknown. Here we analyse circulating tumour cells from 19 women with ER(+)/HER2(-) primary tumours, 84% of whom had acquired circulating tumour cells expressing HER2...
August 24, 2016: Nature
Vanessa Sue Wacleche, Jean-Philippe Goulet, Annie Gosselin, Patricia Monteiro, Hugo Soudeyns, Rémi Fromentin, Mohammad-Ali Jenabian, Shant Vartanian, Steven G Deeks, Nicolas Chomont, Jean-Pierre Routy, Petronela Ancuta
BACKGROUND: Th17 cells are permissive to HIV-1 infection and their depletion from the gut of infected individuals leads to microbial translocation, a major cause for non-AIDS co-morbidities. Most recent evidence supports the contribution of long-lived Th17 cells to HIV persistence during antiretroviral therapy (ART). However, the identity of long-lived Th17 cells remains unknown. RESULTS: Here, we performed an in-depth transcriptional and functional characterization of four distinct Th17 subsets and investigated their contribution to HIV reservoir persistence during ART...
2016: Retrovirology
Chien-Chin Chen, Kung-Chao Chang, L Jeffrey Medeiros, Julia Yu-Yun Lee
BACKGROUND: Hydroa vacciniforme (HV) is associated with Epstein-Barr virus (EBV) infection and a risk of transformation to lymphoma. METHODS: We retrospectively analyzed 6 HV cases for EBV association and transformation to HV-like T-cell lymphoma. Clinicopathologic features were reviewed and cases were assessed for EBV-encoded RNA (EBER) by in situ hybridization, double staining with immunohistochemistry and EBER, and for T-cell clonality. RESULTS: The male-to-female ratio was 5:1, with a median age at diagnosis of 18...
August 17, 2016: Journal of Cutaneous Pathology
Rafal Kaminski, Yilan Chen, Julian Salkind, Ramona Bella, Won-Bin Young, Pasquale Ferrante, Jonathan Karn, Thomas Malcolm, Wenhui Hu, Kamel Khalili
The CRISPR/Cas9 gene editing method is comprised of the guide RNA (gRNA) to target a specific DNA sequence for cleavage and the Cas9 endonuclease for introducing breaks in the double-stranded DNA identified by the gRNA. Co-expression of both a multiplex of HIV-1-specific gRNAs and Cas9 in cells results in the modification and/or excision of the segment of viral DNA, leading to replication-defective virus. In this study, we have personalized the activity of CRISPR/Cas9 by placing the gene encoding Cas9 under the control of a minimal promoter of HIV-1 that is activated by the HIV-1 Tat protein...
2016: Scientific Reports
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