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Double negative T cells

Janine S Hähnlein, Reza Nadafi, Tineke de Jong, Tamara H Ramwadhdoebe, Johanna F Semmelink, Karen I Maijer, IJsbrand A Zijlstra, Mario Maas, Danielle M Gerlag, Teunis B H Geijtenbeek, Paul P Tak, Reina E Mebius, Lisa G M van Baarsen
BACKGROUND: Systemic autoimmunity can be present years before clinical onset of rheumatoid arthritis (RA). Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) regulate immune responses through their intimate connection with leucocytes. We postulate that malfunctioning of LNSCs creates a microenvironment in which normal immune responses are not properly controlled, possibly leading to autoimmune disease. In this study we established an experimental model for studying the functional capacities of human LNSCs during RA development...
February 26, 2018: Arthritis Research & Therapy
Gangqing Hu, Kairong Cui, Difeng Fang, Satoshi Hirose, Xun Wang, Darawalee Wangsa, Wenfei Jin, Thomas Ried, Pentao Liu, Jinfang Zhu, Ellen V Rothenberg, Keji Zhao
How chromatin reorganization coordinates differentiation and lineage commitment from hematopoietic stem and progenitor cells (HSPCs) to mature immune cells has not been well understood. Here, we carried out an integrative analysis of chromatin accessibility, topologically associating domains, AB compartments, and gene expression from HSPCs to CD4+ CD8+ T cells. We found that abrupt genome-wide changes at all three levels of chromatin organization occur during the transition from double-negative stage 2 (DN2) to DN3, accompanying the T lineage commitment...
February 20, 2018: Immunity
Upasana Kulkarni, Christoph Herrmenau, Stephanie J Win, Michael Bauer, Thomas Kamradt
Immunological dysregulation in sepsis is associated with often lethal secondary infections. Loss of effector cells and an expansion of immunoregulatory cell populations both contribute to sepsis-induced immunosuppression. The extent and duration of this immunosuppression are unknown. Interleukin 7 (IL-7) is important for the maintenance of lymphocytes and can accelerate the reconstitution of effector lymphocytes in sepsis. How IL-7 influences immunosuppressive cell populations is unknown. We have used the mouse model of peritoneal contamination and infection (PCI) to investigate the expansion of immunoregulatory cells as long-term sequelae of sepsis with or without IL-7 treatment...
2018: PloS One
Philippe Conus, Larry J Seidman, Margot Fournier, Lijing Xin, Martine Cleusix, Philipp S Baumann, Carina Ferrari, Ann Cousins, Luis Alameda, Mehdi Gholam-Rezaee, Philippe Golay, Raoul Jenni, T-U Wilson Woo, Matcheri S Keshavan, Chin B Eap, Joanne Wojcik, Michel Cuenod, Thierry Buclin, Rolf Gruetter, Kim Q Do
Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC's impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSHmPFC], blood cells GSH levels [GSHBC], GSH peroxidase activity [GPxBC])...
February 15, 2018: Schizophrenia Bulletin
Lara A Aqrawi, Margarita Ivanchenko, Albin Björk, Jorge I Ramírez Sepúlveda, Juliana Imgenberg-Kreuz, Marika Kvarnström, Philipp Haselmayer, Janicke Liaaen Jensen, Gunnel Nordmark, Karine Chemin, Kathrine Skarstein, Marie Wahren-Herlenius
Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. CXCR5 is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand CXCL13. We here aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay...
February 17, 2018: Clinical and Experimental Immunology
Sara M Centuori, Cecil J Gomes, Samuel S Kim, Charles W Putnam, Brandon T Larsen, Linda L Garland, David W Mount, Jesse D Martinez
BACKGROUND: The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A + CD27 - IgD - ...
February 15, 2018: Journal of Translational Medicine
Alexander Fichtner, Caner Süsal, Claudia Schröder, Britta Höcker, Susanne Rieger, Rüdiger Waldherr, Jens H Westhoff, Anja Sander, Duska Dragun, Burkhard Tönshoff
Background: We analysed in a carefully phenotyped cohort of paediatric patients the association of serum angiotensin II type 1 receptor antibodies (AT1R-Ab) with specific histological lesions and with graft function and survival in conjunction with overall and complement-binding donor-specific human leucocyte antigen donor-specific antibodies (HLA-DSA). Methods: Sera of 62 patients at the time of renal graft biopsy for clinical indication >1 year post-transplant were assessed for AT1R-Ab by enzyme-linked immunosorbent assay (ELISA) and for DSA and C1q-fixing DSA by single-antigen bead technology...
February 12, 2018: Nephrology, Dialysis, Transplantation
Ana Risco, Miguel A Martin-Serrano, Domingo F Barber, Ana Cuenda
p38 mitogen-activated protein kinase (MAPK) signal transduction pathways are essential regulators of the immune response. Particularly, p38γ and p38δ regulate many immune cell functions such as cytokine production, migration, or T cell activation; however, their involvement in immune cell development is largely unknown. Here, we analysed the role of p38 MAPK isoforms p38γ and p38δ in T cell differentiation in the thymus and in lymph nodes, using mice deficient in p38γ, p38δ, or in both. We found that the T cell differentiation program in the thymus was affected at different stages in p38γ-, p38δ-, and p38γ/δ-deficient mice, and also peripheral T cell homaeostasis was compromised...
2018: Frontiers in Immunology
Putu Virgina Partha Devanthi, Hani El Kadri, Allen Bowden, Fotios Spyropoulos, Konstantinos Gkatzionis
Antagonism in mixed culture fermentation can result in undesirable metabolic activity and negatively affect the fermentation process. Water-oil-water (W1/O/W2) double emulsions (DE) could be utilized in fermentation for segregating multiple species and controlling their release and activity. Zygosaccharomyces rouxii and Tetragenococcus halophilus, two predominant microbial species in soy sauce fermentation, were incorporated in the internal W1 and external W2 phase of a W1/O/W2, respectively. The suitability of DE for controlling T...
March 2018: Food Research International
Réka Kugyelka, Zoltán Kohl, Katalin Olasz, Lilla Prenek, Tímea Berki, Péter Balogh, Ferenc Boldizsár
The tyrosine kinase ZAP-70 (zeta-chain associated protein of 70 kDa) plays a key role in T cell development and signaling. In the absence of ZAP-70, T cell development is arrested in the CD4+ CD8+ double positive stage, thus ZAP-70 homozygous knockout (ZAP-70-/- ) mice have no mature T cells in their peripheral lymphoid organs and blood, causing severe immunodeficiency. We investigated the early kinetics and long-term effects of wild-type thymocyte transfer on T cell repopulation in ZAP-70-/- mice. We used a single intraperitoneal (ip...
February 12, 2018: Clinical and Experimental Immunology
Georgia Vasileiou, Silvia Vergarajauregui, Sabine Endele, Bernt Popp, Christian Büttner, Arif B Ekici, Marion Gerard, Nuria C Bramswig, Beate Albrecht, Jill Clayton-Smith, Jenny Morton, Susan Tomkins, Karen Low, Astrid Weber, Maren Wenzel, Janine Altmüller, Yun Li, Bernd Wollnik, George Hoganson, Maria-Renée Plona, Megan T Cho, Christian T Thiel, Hermann-Josef Lüdecke, Tim M Strom, Eduardo Calpena, Andrew O M Wilkie, Dagmar Wieczorek, Felix B Engel, André Reis
Variants affecting the function of different subunits of the BAF chromatin-remodelling complex lead to various neurodevelopmental syndromes, including Coffin-Siris syndrome. Furthermore, variants in proteins containing PHD fingers, motifs recognizing specific histone tail modifications, have been associated with several neurological and developmental-delay disorders. Here, we report eight heterozygous de novo variants (one frameshift, two splice site, and five missense) in the gene encoding the BAF complex subunit double plant homeodomain finger 2 (DPF2)...
February 5, 2018: American Journal of Human Genetics
D Brandt, C M Hedrich
TCRαβ+CD3+CD4-CD8-"double negative" (DN) T cells comprise a small subset of mature peripheral T cells. The origin and function of DN T cells are somewhat unclear and discussed controversially. While DN T cells resemble a rare and heterogeneous T cell subpopulation in healthy individuals, numbers of TCRαβ+DN T cells are expanded in several inflammatory conditions, where they also exhibit distinct effector phenotypes and infiltrate inflamed tissues. Thus, DN T cells may be involved in systemic inflammation and tissue damage in autoimmune/inflammatory conditions, including SLE, Sjögren's syndrome, and psoriasis...
February 8, 2018: Autoimmunity Reviews
Allison Voisin, Marjorie Whitfield, Christelle Damon-Soubeyrand, Chantal Goubely, Joëlle Henry-Berger, Fabrice Saez, Ayhan Kocer, Joël R Drevet, Rachel Guiton
Despite increasing evidence that epididymal immune disorders can lead to infertility, the cells and mechanisms underlying epididymal immunity remain poorly understood. In this study, we propose a rather exhaustive overview of innate and adaptive immune cells present in the murine caput and cauda epididymis. Using flow cytometry and a wide set of markers, we screened the broadest panel of immune cells ever, in this organ. For the first time, we unequivocally quantified the innate populations of monocytes, macrophages, and dendritic cells subtypes...
January 31, 2018: Journal of Reproductive Immunology
L F da Rosa Franchi Santos, N P Stadtlober, L G Costa Dall'Aqua, B M Scavuzzi, P M Guimarães, T Flauzino, M A Batisti Lozovoy, T V Mayumi Iriyoda, E M Vissoci Reiche, I Dichi, M Maes, A Colado Simão
Background This study was performed to assess adhesion molecules in systemic lupus erythematosus (SLE). Methods This case-control study examined 126 SLE patients and 48 healthy individuals. Blood levels of six adhesion molecules, cortisol, nuclear autoantibody (ANA) and anti-double stranded DNA (anti-dsDNA) titers were measured, while disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, P-selectin, and plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients than in controls...
January 1, 2018: Lupus
Yoichi Kakuta, Shigeru Satoh, Yoshihiko Watarai, Atsushi Aikawa, Kazunari Tanabe, Hiroshi Harada, Takashi Yagisawa, Hideki Ishida, Masayoshi Okumi, Shiro Takahara
Background: High-dose IVIG (2 g/kg) alone or low-dose IVIG (100 mg/kg) in conjunction with plasma exchange is typically administered as a renal transplantation desensitization therapy. Herein, we monitored changes in T cell and B cell flow cytometry crossmatch (FCXM) to assess the effects of short-term super high-dose IVIG (4 g/kg) administration with plasmapheresis before living-donor renal transplantation. Methods: Seventeen patients, each showing positive T cell FCXM (median ratio, ≥ 1...
January 2018: Transplantation Direct
Nouf Al-Subhi, Reem Ali, Tarek Abdel-Fatah, Paul M Moseley, Stephen Y T Chan, Andrew R Green, Ian O Ellis, Emad A Rakha, Srinivasan Madhusudan
PURPOSE: Phosphate and tensin homolog (PTEN), a negative regulator of PI3K signaling, is involved in DNA repair. ATR is a key sensor of DNA damage and replication stress. We evaluated whether ATR signaling has clinical significance and could be targeted by synthetic lethality in PTEN-deficient triple-negative breast cancer (TNBC). METHODS: PTEN, ATR and pCHK1Ser345 protein level was evaluated in 1650 human breast cancers. ATR blockade by VE-821 was investigated in PTEN-proficient- (MDA-MB-231) and PTEN-deficient (BT-549, MDA-MB-468) TNBC cell lines...
February 2, 2018: Breast Cancer Research and Treatment
Christopher Grunseich, Isabel X Wang, Jason A Watts, Joshua T Burdick, Robert D Guber, Zhengwei Zhu, Alan Bruzel, Tyler Lanman, Kelian Chen, Alice B Schindler, Nancy Edwards, Abhik Ray-Chaudhury, Jianhua Yao, Tanya Lehky, Grzegorz Piszczek, Barbara Crain, Kenneth H Fischbeck, Vivian G Cheung
R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway...
February 1, 2018: Molecular Cell
Alessandra Torina, Giuliana Guggino, Marco Pio La Manna, Guido Sireci
Natural killer T cells (NKT) are a subset of T lymphocytes bridging innate and adaptive immunity. These cells recognize self and microbial glycolipids bound to non-polymorphic and highly conserved CD1d molecules. Three NKT cell subsets, type I, II, and NKT-like expressing different antigen receptors (TCR) were described and TCR activation promotes intracellular events leading to specific functional activities. NKT can exhibit different functions depending on the secretion of soluble molecules and the interaction with other cell types...
February 1, 2018: International Journal of Molecular Sciences
Anna E Coghill, Jeannette M Schenk, Zeina Mahkoul, Jackson Orem, Warren Phipps, Corey Casper
OBJECTIVE: Kaposi sarcoma is a HIV-associated malignancy caused by human herpesvirus-8 (HHV-8) that occurs at highest incidence in sub-Saharan Africa. Kaposi sarcoma patients often present with inflammatory symptoms associated with higher mortality. DESIGN: We conducted a double-blind, randomized, placebo-controlled study in Uganda to test whether omega-3 supplementation could reduce inflammation in HIV and HHV-8 coinfected adults. Patients with acute illness, AIDS, or advanced Kaposi sarcoma were ineligible, as were pregnant women...
February 20, 2018: AIDS
Sotaro Ochiai, Ferdinand Jagot, Ryan L Kyle, Evelyn Hyde, Ruby F White, Melanie Prout, Alfonso J Schmidt, Hidehiro Yamane, Olivier Lamiable, Graham Le Gros, Franca Ronchese
T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4+ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4+ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4+ T cells; TSLP and Th2 conditions were both required for their development...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
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