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https://www.readbyqxmd.com/read/29150704/evaluation-of-immune-mediated-idiosyncratic-drug-toxicity-using-chimeric-hla-transgenic-mice
#1
Takeshi Susukida, Shigeki Aoki, Kotaro Kogo, Sota Fujimori, Binbin Song, Cong Liu, Shuichi Sekine, Kousei Ito
Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT...
November 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29135655/neutrophil-activation-and-enhanced-release-of-granule-products-in-hiv-tb-immune-reconstitution-inflammatory-syndrome
#2
Justine K Nakiwala, Naomi F Walker, Collin R Diedrich, William Worodria, Graeme Meintjes, Robert J Wilkinson, Harriet Mayanja-Kizza, Robert Colebunders, Luc Kestens, Katalin A Wilkinson, David M Lowe
BACKGROUND: Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and in particular the role of neutrophils. SETTING: Two observational, prospective cohort studies in HIV/TB co-infected patients starting antiretroviral therapy, one to analyze gene expression and subsequently one to explore neutrophil biology...
November 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29129997/trichloroethylene-induced-alterations-in-dna-methylation-were-enriched-in-polycomb-protein-binding-sites-in-effector-memory-cd4-t-cells
#3
Kathleen M Gilbert, Sarah J Blossom, Brad Reisfeld, Stephen W Erickson, Kanan Vyas, Mary Maher, Brannon Broadfoot, Kirk West, Shasha Bai, Craig A Cooney, Sudeepa Bhattacharyya
Exposure to industrial solvent and water pollutant trichloroethylene (TCE) can promote autoimmunity, and expand effector/memory (CD62L) CD4(+) T cells. In order to better understand etiology reduced representation bisulfite sequencing was used to study how a 40-week exposure to TCE in drinking water altered methylation of ∼337 770 CpG sites across the entire genome of effector/memory CD4(+) T cells from MRL+/+ mice. Regardless of TCE exposure, 62% of CpG sites in autosomal chromosomes were hypomethylated (0-15% methylation), and 25% were hypermethylated (85-100% methylation)...
July 2017: Environmental Epigenetics
https://www.readbyqxmd.com/read/29115434/n-butanol-extract-from-folium%C3%A2-isatidis-inhibits-the-lipopolysaccharide-induced-downregulation-of-cxcr1-and-cxcr2-on-human-neutrophils
#4
Beibei Wu, Liyin Wang, Lili Jiang, Lili Dong, Fengli Xu, Yili Lu, Jiahui Jin, Zhanyue Wang, Guang Liang, Xiaoou Shan
Neutrophils, immune cells crucial for protecting against invading pathogens, are important in sepsis. Neutrophil migration is regulated by chemokine receptors and their cognate ligands. Our previous study investigated the effect of n‑butanol extract from Folium isatidis on lipopolysaccharide (LPS)‑induced septic shock. The present study stimulated neutrophils with LPS to explore the influence of LPS on cell. Neutrophils were then pretreated with n‑butanol extract from Folium isatidis followed by LPS to examine the effect of this extract on neutrophil chemotaxis...
October 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29104081/wnt-pathway-activator-tws119-enhances-the-proliferation-and-cytolytic-activity-of-human-%C3%AE-%C3%AE-t-cells-against-colon-cancer
#5
Yong-Qiang Chen, Lu Zheng, Mohanad Aldarouish, Zhong-Hai Zhou, Ning Pan, Jun-Quan Liu, Fu-Xing Chen, Li-Xin Wang
γδT cells are a distinct T-cell subset that display unique characteristics regarding T-cell receptor gene usage, tissue tropism and antigen recognition. Adoptive γδT cell transfer therapy has recently been gaining importance as an efficient approach in cancer immunotherapy. However, exploiting γδT cell response for tumour immunotherapy is a challenge due to cell numbers, activities and differentiation states that minimize the clinical therapeutic effects. Previous studies have indicated that the wnt/β-catenin signalling pathway plays a crucial role in the differentiation, survival and enhancement of the immune response of T lymphocytes...
November 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29093987/targeting-the-epitope-spreader-pep19-by-na%C3%A3-ve-human-cd45ra-regulatory-t-cells-dictates-a-distinct-suppressive-t-cell-fate-in-a-novel-form-of-immunotherapy
#6
Hyun-Joo Kim, Gil Sun Cha, Ji-Young Joo, Juyoun Lee, Sung-Jo Kim, Jeongae Lee, So Youn Park, Jeomil Choi
Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal CD4(+)CD25(+)CD127(lo-) Tregs (127-Tregs) and naïve CD4(+)CD25(+)CD45RA(+) Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion...
October 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/29092860/exercise-training-reverses-inflammation-and-muscle-wasting-after-tobacco-smoke-exposure
#7
Karsten Krüger, Michael Seimetz, Robert Ringseis, Jochen Wilhelm, Alexandra Pichl, Aline Couturier, Klaus Eder, Norbert Weissmann, Frank C Mooren
Long term cigarette smoking induces inflammatory processes in the pulmonary system which are suggested to "spill over" into systemic inflammation. Regular exercise has been shown to have anti-inflammatory properties. The aim of the study was to investigate the effects of therapeutic exercise on inflammation and muscle wasting in smoke-exposed mice. C57BL/6J-mice (n = 30) were separated into three groups to receive either: (1) controls with no specific treatment (Con group), (2) 8 months exposure to cigarette smoke (smoke-exposed (SE) group), (3) 8 months of cigarette smoke combined with exercise training during the last 2 months (SEex group)...
November 1, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29050459/third-party-regulatory-t-cells-prevent-murine-acute-graft-versus-host-disease
#8
Jung-Yeon Lim, Keon-Il Im, Yunejin Song, Nayoun Kim, Young-Sun Nam, Young-Woo Jeon, Seok-Goo Cho
Background/Aims: Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention...
October 19, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29040326/mycobacterium-tuberculosis-infection-modulates-adipose-tissue-biology
#9
Macarena Beigier-Bompadre, Georgina N Montagna, Anja A Kühl, Laura Lozza, January Weiner, Andreas Kupz, Alexis Vogelzang, Hans-Joachim Mollenkopf, Delia Löwe, Silke Bandermann, Anca Dorhoi, Volker Brinkmann, Kai Matuschewski, Stefan H E Kaufmann
Mycobacterium tuberculosis (Mtb) primarily resides in the lung but can also persist in extrapulmonary sites. Macrophages are considered the prime cellular habitat in all tissues. Here we demonstrate that Mtb resides inside adipocytes of fat tissue where it expresses stress-related genes. Moreover, perigonadal fat of Mtb-infected mice disseminated the infection when transferred to uninfected animals. Adipose tissue harbors leukocytes in addition to adipocytes and other cell types and we observed that Mtb infection induces changes in adipose tissue biology depending on stage of infection...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29033940/pi3k%C3%AE-inhibition-enhances-the-antitumor-fitness-of-adoptively-transferred-cd8-t-cells
#10
Jacob S Bowers, Kinga Majchrzak, Michelle H Nelson, Bulent Arman Aksoy, Megan M Wyatt, Aubrey S Smith, Stefanie R Bailey, Lillian R Neal, Jeffrey E Hammerbacher, Chrystal M Paulos
Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8(+) T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29032059/is-the-adaptive-immune-response-in-murine-trypanosoma-cruzi-infection-influenced-by-zinc-supplementation
#11
Cássia Mariana Bronzon da Costa, Marina Del Vecchio Filipin, Fabrícia Helena Santello, Luiz Miguel Pereira, Miriam Paula Alonso Toldo, José Clóvis do Prado Júnior, Ana Amélia Carraro Abrahão
Chagas disease afflicts 7 to 8 million people worldwide and congenital Chagas' disease usually leads to changes in the maternal environment, culminating in fetal adaptations. Several articles have described the importance of micronutrients on pregnancy, which is sensitive to infections. In Trypanosoma cruzi endemic regions, the Chagas disease is aggravated by the lack of micronutrients in an average diet, to which pregnant women are more susceptible. The aim of this study was to evaluate distinct T cells phenotypes and intracellular cytokines by flow cytometry in pregnant Wistar rats under zinc therapy during experimental Chagas' disease...
October 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29023759/cord-blood-derived-t-cells-allow-the-generation-of-a-more-na%C3%A3-ve-tumor-reactive-cytotoxic-t-cell-phenotype
#12
Julian Kwoczek, Sebastian B Riese, Sabine Tischer, Szilvia Bak, Julia Lahrberg, Mathias Oelke, Holger Maul, Rainer Blasczyk, Martin Sauer, Britta Eiz-Vesper
BACKGROUND: Transplantation of hematopoietic stem cells (HSCs) from peripheral blood (PB) or cord blood (CB) is well established. HSCs from CB are associated with a lower risk of graft-versus-host disease (GVHD), but antigen-independent expanded CB- and PB-derived T cells can induce GVHD in allo-HSC recipients. CB-derived cells might be more suitable for adoptive immunotherapy as they have unique T-cell characteristics. Here, we describe functional differences between CB and PB T cells stimulated with different cytokine combinations involved in central T-cell activation...
October 11, 2017: Transfusion
https://www.readbyqxmd.com/read/28993768/cd30-is-dispensable-for-t-cell-responses-to-influenza-virus-and-lymphocytic-choriomeningitis-virus-clone-13-but-contributes-to-age-associated-t-cell-expansion-in-mice
#13
Angela C Zhou, Laura M Snell, Michael E Wortzman, Tania H Watts
CD30 is a tumor necrosis factor receptor (TNFR) family member whose expression is associated with Hodgkin's disease, anaplastic large cell lymphomas, and other T and B lymphoproliferative disorders in humans. A limited number of studies have assessed the physiological role of CD30/CD30 ligand interactions in control of infection in mice. Here, we assess the role of CD30 in T-cell immunity to acute influenza and chronic lymphocytic choriomeningitis virus (LCMV) clone 13 infection, two viral infections in which other members of the TNFR superfamily are important for T-cell responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28987000/microrna-126-deficiency-enhanced-the-activation-and-function-of-cd4-t-cells-by-elevating-irs-1-pathway
#14
Fengyun Chu, Yan Hu, Ya Zhou, Mengmeng Guo, Jia Lu, Wen Zheng, Hualin Xu, Juanjuan Zhao, Lin Xu
Recent evidence showed that microRNA-126 (miR-126) has been involved in the development and function of immune cells, which contributed to the pathogenesis of related clinical diseases. However, the potential role of miR-126 in the development and function of CD4(+) T cells remains largely unknown. Here we firstly found that the activation and proliferation, as well as the expression of IFN-γ, of CD4(+) T cells from miR-126 knockdown (KD) mice using miRNA-Sponge technique were enhanced significantly in vitro, compared with those in CD4(+) T cells from wild type (WT) mice...
October 7, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28986344/nk-cell-recovery-after-haploidentical-hsct-with-post-transplant-cyclophosphamide-dynamics-and-clinical-implications
#15
Antonio Russo, Giacomo Oliveira, Sofia Berglund, Raffaella Greco, Valentina Gambacorta, Nicoletta Cieri, Cristina Toffalori, Laura Zito, Francesca Lorentino, Simona Piemontese, Mara Morelli, Fabio Giglio, Andrea Assanelli, Maria Teresa Lupo Stanghellini, Chiara Bonini, Jacopo Peccatori, Fabio Ciceri, Leo Luznik, Luca Vago
The use of post-transplant cyclophosphamide (PT-Cy) as GvHD prophylaxis has revolutionized haploidentical HSCT, allowing safe infusion of unmanipulated T cell-replete grafts. PT-Cy selectively eliminates proliferating alloreactive T cells, but whether and how it affects NK cells and their alloreactivity is largely unknown. Here we characterized NK cell dynamics in 17 patients who received unmanipulated haploidentical grafts, containing high numbers of mature NK cells, according to PT-Cy-based protocols in two independent centers...
October 6, 2017: Blood
https://www.readbyqxmd.com/read/28985739/a-lipidated-peptide-of-mycobacterium-tuberculosis-resuscitates-the-protective-efficacy-of-bcg-vaccine-by-evoking-memory-t-cell-immunity
#16
Pradeep K Rai, Sathi Babu Chodisetti, Weiguang Zeng, Sajid Nadeem, Sudeep K Maurya, Susanta Pahari, Ashok K Janmeja, David C Jackson, Javed N Agrewala
BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28985649/peripheral-blood-mononuclear-cell-immunophenotyping-in-fibrodysplasia-ossificans-progressiva-patients-evidence-for-monocyte-dnam1-up-regulation
#17
Genny Del Zotto, Francesca Antonini, Irma Azzari, Claudio Ortolani, Gino Tripodi, Francesca Giacopelli, Serena Cappato, Lorenzo Moretta, Roberto Ravazzolo, Renata Bocciardi
Background Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disorder caused by sporadic heterozygous mutations in ACVR1 gene which progressively leads to severe heterotopic ossification. FOP is characterized by episodic flare-ups triggered by different factors such as viral infections, tissue injuries, vaccinations or occurring without a recognizable cause. The sporadic course of the disease, the documented presence of an important inflammatory reaction in early lesions and the partial response to corticosteroids support the idea that the immune system, and in particular the innate component, may play a role in FOP pathogenesis...
October 6, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28951779/cd4-t-cells-and-natural-killer-cells-biomarkers-for-hepatic-fibrosis-in-human-immunodeficiency-virus-hepatitis-c-virus-coinfected-patients
#18
Natalia Laufer, Diego Ojeda, María Laura Polo, Ana Martinez, Héctor Pérez, Gabriela Turk, Pedro Cahn, Norberto Walter Zwirner, Jorge Quarleri
AIM: To characterize peripheral blood natural killer (NK) cells phenotypes by flow cytometry as potential biomarker of liver fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients. METHODS: Peripheral mononuclear cells from 24 HIV/HCV (HBV negative) coinfected and 5 HIV/HCV/HBV seronegative individuals were evaluated. HIV/HCV coinfected patients were divided in to groups: G1, patients with METAVIR F0-F2 and G2, patients with METAVIR F3-F4...
September 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28947964/chinese-medicine-ginseng-and-astragalus-granules-ameliorate-autoimmune-diabetes-by-upregulating-both-cd4-foxp3-and-cd8-cd122-pd1-regulatory-t-cells
#19
Yeshu Wang, Qingfeng Xie, Chun-Ling Liang, Qiaohuang Zeng, Zhenhua Dai
Type 1 diabetes mellitus (T1DM) is an autoimmune disease mainly mediated by effector T cells that are activated by autoantigen, thereby resulting in the destruction of pancreatic islets and deficiency of insulin. Cyclosporine is widely used as an immunosuppressant that suppresses autoimmunity in clinic. However, continuous treatments with conventional immunosuppressive drugs may cause severe side effects. Therefore it is important to seek alternative medicine. Chinese medicine Ginseng and Astragalus granule (GAG) was used to successfully treat type 2 diabetes mellitus in clinic in China...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904691/il-21-augments-rapamycin-in-expansion-of-alpha-fetoprotein-antigen-specific-stem-cell-like-memory-t-cells-in-vitro
#20
Victor Tunje Jeza, Xiaoyi Li, Jun Chen, Zhihui Liang, Adem Onago Aggrey, Xiongwen Wu
INTRODUCTION: Alloreactive tumor specific T cells are important arsenals of the adaptive immune system in the fight against tumors. However, stem cell-like memory T cells (Tscm) provide the key to effective elimination of tumor cells. Methods for generating these T cell subsets already exist. However, they could be made more efficient. Further, they are expensive and unattainable to the resource poor laboratories. In this regard, we are hereby describing a novel in vitro allogeneic co-culture method for raising allo-restricted tumor specific Tscm cells that we developed...
2017: Pan African Medical Journal
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