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https://www.readbyqxmd.com/read/27921403/prognostic-significance-of-regulatory-t-lymphocytes-in-patients-with-hepatocellular-carcinoma
#1
Ai-Bin Zhang, Yi-Gang Qian, Shu-Sen Zheng
We investigated the prognostic role of regulatory T cells (Tregs) in patients with hepatocellular carcinoma (HCC). Relevant evidence regarding prognostic significance of Tregs was systematically searched in MEDLINE and Embase databases. A meta-analysis was performed to compare survival in patients with high or low Tregs level (either in peripheral blood or tumor). Eighteen studies were identified that fulfilled for the eligibility criteria and were included for data synthesis. Our pooled hazard ratios (HRs) demonstrated that increased Tregs intratumoral accumulation was significantly associated with worse overall survival (HR=2...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27913516/immunoregulatory-networks-in-sickle-cell-alloimmunization
#2
Karina Yazdanbakhsh
Red blood cell (RBC) transfusions are critical for treatment and prevention of complications of sickle cell disease (SCD), and most SCD patients will receive 1 or more transfusions by age 20. However, SCD alloimmunization remains a serious complication of transfusions that can lead to life-threatening acute and delayed transfusion reactions. Alloimmunization rates are higher in SCD patients most likely due to RBC antigenic differences between largely white donors vs mainly African-American recipients and frequency of transfusions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912146/inosine-acedoben-dimepranol-promotes-an-early-and-sustained-increase-in-the-natural-killer-cell-component-of-circulating-lymphocytes-a-clinical-trial-supporting-anti-viral-indications
#3
S Rumel Ahmed, Amy S Newman, James O'Daly, Sean Duffy, Gillian Grafton, Catherine A Brady, S John Curnow, Nicholas M Barnes, John Gordon
Inosine Acedoben Dimepranol (IAD), licensed for the treatment of cell-mediated immune deficiencies associated with viral infections, has been reported to impact a variety of immune parameters both in vitro and in vivo. Here we report the results from a clinical trial where multiple lymphocyte subsets - CD19+ B cells, CD3+ T cells, CD4+ T-helper cells, FoxP3(hi)/CD25(hi)/CD127(lo) regulatory T cells (Tregs), CD3-/CD56+ NK cells, and CD3+/CD56+ NKT cells - were, together with serum immunoglobulins and IgG subclasses, followed during 14days of IAD administration to ten healthy volunteers; these selected from 27 individuals pre-screened in vitro for their capacity to respond to IAD as gauged by increases in the percentage of Treg and/or NKT cells arising in PHA-stimulated cultures...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27909722/expression-of-soluble-programmed-death-1-protein-in-peripheral-blood-regulatory-t-cells-and-its-effects-on-rheumatoid-arthritis-progression
#4
Chun-Feng Ren, Ya-Xin Zhao, Chun-Feng Hou, Luan Luan, Guo-Qing Duan, Shu-Jie Li, Jian-Hong Zhao
The present study aimed to investigate the role of the soluble programmed death‑1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry...
November 28, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27904448/mobilization-with-cyclophosphamide-reduces-the-number-of-lymphocyte-subpopulations-in-the-leukapheresis-product-and-delays-their-reconstitution-after-autologous-hematopoietic-stem-cell-transplantation-in-patients-with-multiple-myeloma
#5
Matevz Skerget, Barbara Skopec, Darja Zontar, Peter Cernelc
BACKGROUND: Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation...
December 1, 2016: Radiology and Oncology
https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#6
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27902485/impacts-of-cigarette-smoking-on-immune-responsiveness-up-and-down-or-upside-down
#7
REVIEW
Feifei Qiu, Chun-Ling Liang, Huazhen Liu, Yu-Qun Zeng, Shaozhen Hou, Song Huang, Xiaoping Lai, Zhenhua Dai
Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899576/the-nuclear-and-organellar-trna-derived-rna-fragment-population-in-arabidopsis-thaliana-is-highly-dynamic
#8
Valérie Cognat, Geoffrey Morelle, Cyrille Megel, Stéphanie Lalande, Jean Molinier, Timothée Vincent, Ian Small, Anne-Marie Duchêne, Laurence Maréchal-Drouard
In the expanding repertoire of small noncoding RNAs (ncRNAs), tRNA-derived RNA fragments (tRFs) have been identified in all domains of life. Their existence in plants has been already proven but no detailed analysis has been performed. Here, short tRFs of 19-26 nucleotides were retrieved from Arabidopsis thaliana small RNA libraries obtained from various tissues, plants submitted to abiotic stress or fractions immunoprecipitated with ARGONAUTE 1 (AGO1). Large differences in the tRF populations of each extract were observed...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27896283/a-potential-founder-variant-in-carmil2-rltpr-in-three-norwegian-families-with-warts-molluscum-contagiosum-and-t-cell-dysfunction
#9
Hanne S Sorte, Liv T Osnes, Børre Fevang, Pål Aukrust, Hans C Erichsen, Paul H Backe, Tore G Abrahamsen, Ole B Kittang, Torstein Øverland, Shalini N Jhangiani, Donna M Muzny, Magnus D Vigeland, Pubudu Samarakoon, Tomasz Gambin, Zeynep H C Akdemir, Richard A Gibbs, Olaug K Rødningen, Robert Lyle, James R Lupski, Asbjørg Stray-Pedersen
BACKGROUND: Four patients from three Norwegian families presented with a common skin phenotype of warts, molluscum contagiosum, and dermatitis since early childhood, and various other immunological features. Warts are a common manifestation of human papilloma virus (HPV), but when they are overwhelming, disseminated and/or persistent, and presenting together with other immunological features, a primary immunodeficiency disease (PIDD) may be suspected. METHODS AND RESULTS: The four patients were exome sequenced as part of a larger study for detecting genetic causes of primary immunodeficiencies...
November 2016: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/27895398/dysregulation-of-innate-immunity-in-ulcerative-colitis-patients-who-fail-anti-tumor-necrosis-factor-therapy
#10
Angela C Baird, Dominic Mallon, Graham Radford-Smith, Julien Boyer, Thierry Piche, Susan L Prescott, Ian C Lawrance, Meri K Tulic
AIM: To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS: Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders" (n = 12) and "non-responders" (n = 12) and compared to healthy controls (n = 12)...
November 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27893612/the-influence-of-timing-and-frequency-of-adipose-derived-mesenchymal-stem-cell-therapy-on-immunomodulation-outcomes-after-vascularized-composite-allotransplantation
#11
Jan A Plock, Jonas T Schnider, Riccardo Schweizer, Wensheng Zhang, Wakako Tsuji, Matthias Waldner, Mario G Solari, Kacey G Marra, J Peter Rubin, Vijay S Gorantla
BACKGROUND: Cellular therapies for immunomodulation in vascularized composite allotransplantation (VCA) have gained importance due to their potential minimization of immunosuppression. Adipose-derived mesenchymal stem cells (AD-MSCs) especially have shown encouraging potential. We investigated the influence of timing and frequency of AD-MSC-treatment on immunologic and graft survival as well as graft vasculopathy (GV) outcomes after VCA. METHODS: Lewis (LEW) rats received full-mismatched Brown Norway (BN) rat hindlimb transplants...
November 23, 2016: Transplantation
https://www.readbyqxmd.com/read/27886644/oral-administration-with-diosgenin-enhances-the-induction-of-intestinal-t-helper-1-like-regulatory-t-cells-in-a-murine-model-of-food-allergy
#12
Chung-Hsiung Huang, Chia-Chi Wang, Yu-Chin Lin, Masatoshi Hori, Tong-Rong Jan
Although the development of T helper (Th)1-like regulatory T (Treg) cells under Th1 inflammatory conditions has been reported, the role of Th1-like Treg cells in Th2 allergic responses remains mostly unclear. We previously demonstrated that diosgenin, the major sapogenin contained in the Chinese yam, attenuated food allergy and augmented Th1 and Treg immune responses. In this study, we hypothesized that diosgenin may enhance the induction of Th1-like Treg cells in the gut of mice with food allergy. Ovalbumin (OVA)-sensitized BALB/c mice were gavaged daily with diosgenin and received repeatedly intragastric ovalbumin challenges to induce intestinal allergic responses...
November 23, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27882473/foxp3-regulatory-t-cell-and-autoimmune-diseases
#13
REVIEW
Jin-Hui Tao, Miao Cheng, Jiang-Ping Tang, Qin Liu, Fan Pan, Xiang-Pei Li
Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases. Therefore, therapeutic modulation of Tregs could be a potent means of treating autoimmune diseases. Human Tregs are diverse, however, and not all of them have immunosuppressive effects. Forkhead box P3 (Foxp3), a pivotal transcription factor of Tregs that is crucial in maintaining Treg immunosuppressive function, can be expressed heterogeneously or unstably across Treg subpopulations...
November 24, 2016: Inflammation
https://www.readbyqxmd.com/read/27880975/ror%C3%AE-t-expression-in-tregs-promotes-systemic-lupus-erythematosus-via-il-17-secretion-alteration-of-treg-phenotype-and-suppression-of-th2-responses
#14
Malte A Kluger, Anna Nosko, Torben Ramcke, Boeren Goerke, Matthias C Meyer, Claudia Wegscheid, Michael Luig, Gisa Tiegs, Rolf A K Stahl, Oliver M Steinmetz
Systemic lupus erythematosus (SLE) is a common autoimmune disorder with a complex and poorly understood immuno-pathogenesis. However, a pathogenic role for the Th17 axis was demonstrated by many studies, while Tregs were shown to mediate protection. Recently, we and others characterized a novel and independent T cell population expressing both, the Treg characteristic transcription factor Foxp3 and the Th17 defining RORγt. Studies in a model of acute glomerulonephritis unveiled potent regulatory, but in addition also pro-inflammatory functions of RORγt(+) Foxp3(+) Tregs...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27880974/deep-sequencing-of-the-tcrb-repertoire-of-human-foxp3-and-foxp3-t-cells-suggests-that-they-are-completely-distinct-and-non-overlapping
#15
Amit Golding, Samuel Darko, William H Wylie, Daniel C Douek, Ethan M Shevach
Maintenance of peripheral tolerance requires a balance between auto-reactive conventional T cells (Tconv) and thymically-derived Foxp3(+) regulatory T cells (tTregs). Considerable controversy exists regarding the similarities/differences in TCR repertoires expressed by Tconv and tTregs. We generated highly purified populations of human adult and cord blood Tconv and tTregs based on the differential expression of CD25 and CD127. The purity of the sorted populations was validated by intracellular staining for Foxp3 and Helios...
November 23, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27880796/foxn1-cre-expression-in-the-male-germline
#16
Jianjun Shi, Irina Getun, Bivian Torres, Howard T Petrie
Foxn1 (forkhead box N1), also known as the nude gene or winged-helix nude (Whn), is a forkhead transcription factor thought to be restricted to keratinocytes in the skin and thymus. Consistent with this tissue distribution, spontaneous or targeted mutation of Foxn1 results in the absence of both hair and a thymus. Genetic manipulation of the Foxn1 locus thus represents a powerful tool for tissue specific gene control in the skin and thymus, and tools such as Cre recombinase under control of the Foxn1 locus are widely used for this purpose...
2016: PloS One
https://www.readbyqxmd.com/read/27873300/local-checkpoint-inhibition-of-ctla-4-as-a-monotherapy-or-in-combination-with-anti-pd1-prevents-the-growth-of-murine-bladder-cancer
#17
Luuk van Hooren, Linda C Sandin, Igor Moskalev, Peter Ellmark, Anna Dimberg, Peter Black, Thomas H Tötterman, Sara M Mangsbo
Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in metastatic cancer patients. However, patients treated with CTLA-4 blockade have suffered from immune related adverse events, most likely due to the breadth of the induced T-cell activation. Here, we investigated the efficacy of a local low-dose anti-CTLA-4 administration for treatment of subcutaneous or orthotopic MB49 bladder carcinoma in C57BL/6 mice. When MB49 tumors were grown subcutaneously, peritumoral injection of anti-CTLA-4 treatment was equally effective as intravenous or subcutaneous (non-tumor bearing flank) administration...
November 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27870570/activating-notch1-mutations-define-a-distinct-subgroup-of-patients-with-adenoid-cystic-carcinoma-who-have-poor-prognosis-propensity-to-bone-and-liver-metastasis-and-potential-responsiveness-to-notch1-inhibitors
#18
Renata Ferrarotto, Yoshitsugu Mitani, Lixia Diao, Irene Guijarro, Jing Wang, Patrick Zweidler-McKay, Diana Bell, William N William, Bonnie S Glisson, Michael J Wick, Ann M Kapoun, Amita Patnaik, Gail Eckhardt, Pamela Munster, Leonardo Faoro, Jakob Dupont, J Jack Lee, Andrew Futreal, Adel K El-Naggar, John V Heymach
Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro...
November 21, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27866707/a-functional-variant-associated-with-atrial-fibrillation-regulates-pitx2c-expression-through-tfap2a
#19
Jiangchuan Ye, Nathan R Tucker, Lu-Chen Weng, Sebastian Clauss, Steven A Lubitz, Patrick T Ellinor
The most significantly associated genetic locus for atrial fibrillation (AF) is in chromosomal region 4q25, where four independent association signals have been identified. Although model-system studies suggest that altered PITX2c expression might underlie the association, the link between specific variants and the direction of effect on gene expression remains unknown for all four signals. In the present study, we analyzed the AF-associated region most proximal to PITX2 at 4q25. First, we identified candidate regulatory variants that might confer AF risk through a combination of mammalian conservation, DNase hypersensitivity, and histone modification from ENCODE and the Roadmap Epigenomics Project, as well as through in vivo analysis of enhancer activity in embryonic zebrafish...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27865176/adoptive-immunotherapy-for-hematological-malignancies-current-status-and-new-insights-in-chimeric-antigen-receptor-t-cells
#20
REVIEW
Alessandro Allegra, Vanessa Innao, Demetrio Gerace, Doriana Vaddinelli, Caterina Musolino
Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors...
November 2016: Blood Cells, Molecules & Diseases
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