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https://www.readbyqxmd.com/read/29425052/regulatory-t-cells-subvert-mycobacterial-containment-in-patients-failing-extensively-drug-resistant-tb-treatment
#1
Malika Davids, Anil S Pooran, Elize Pietersen, Helen C Wainwright, Anke Binder, Robin Warren, Keertan Dheda
RATIONALE: The advent of extensively (XDR-TB) and totally drug-resistant TB, with limited or no treatment options, has facilitated renewed interest in host directed immunotherapy, particularly for therapeutically destitute patients. However, the selection and utility of such approaches depend upon understanding the host immune response in XDR-TB, which hitherto remains unexplored. OBJECTIVES: To determine the host immunological profile in patients with XDR-TB, compared to drug-sensitive TB, using peripheral blood and explanted lung tissue...
February 9, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29414937/c-maf-dependent-regulatory-t-cells-mediate-immunological-tolerance-to-a-gut-pathobiont
#2
Mo Xu, Maria Pokrovskii, Yi Ding, Ren Yi, Christy Au, Oliver J Harrison, Carolina Galan, Yasmine Belkaid, Richard Bonneau, Dan R Littman
Both microbial and host genetic factors contribute to the pathogenesis of autoimmune diseases. There is accumulating evidence that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease, often also colonize healthy individuals. These microorganisms, including the Helicobacter species, can induce pathogenic T cells and are collectively referred to as pathobionts. However, how such T cells are constrained in healthy individuals is not yet understood. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus, is mediated by the induction of RORγt+FOXP3+ regulatory T (iTreg) cells that selectively restrain pro-inflammatory T helper 17 (TH17) cells and whose function is dependent on the transcription factor c-MAF...
February 7, 2018: Nature
https://www.readbyqxmd.com/read/29409398/immune-dysregulation-in-primary-immune-thrombocytopenia-patients
#3
Jiakui Zhang, Qiuye Zhang, Yingwei Li, Lili Tao, Fan Wu, Yuanyuan Shen, Qianshan Tao, Xuanxuan Xu, Can Wu, Yanjie Ruan, Jiyu Wang, Jeffrey Wang, Yiping Wang, Zhimin Zhai
OBJECTIVES: To explore the immunological abnormalities in patients with primary immune thrombocytopenia (ITP), and analyze its relationship with treatment. METHODS: Proportion of different immune cell subsets were detected in the peripheral blood of 124 ITP patients at different time points and 45 normal controls by flow cytometry. The treatments included glucocorticoids, intravenous IgG as first-line treatment and second-line drugs. RESULTS: Elevated CD4/CD8 ratio and decreased the proportion of NK and CD4 + CD25 + CD127low regulatory T cells (Tregs) were found in pre-treated ITP patients than healthy controls...
February 6, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29408453/a-randomized-control-trial-to-establish-the-feasibility-and-safety-of-rapamycin-treatment-in-an-older-human-cohort-immunological-physical-performance-and-cognitive-effects
#4
Ellen Kraig, Leslie A Linehan, Hanyu Liang, Terry Q Romo, Qianqian Liu, Yubo Wu, Adriana D Benavides, Tyler J Curiel, Martin A Javors, Nicolas Musi, Laura Chiodo, Wouter Koek, Jonathan A L Gelfond, Dean L Kellogg
Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that mTOR inhibition could potentially slow the progression of aging-associated pathologies in older humans (Harrison et al., 2009; Miller et al., 2011). However, the safety and tolerability of RAPA in older human subjects have not yet been demonstrated...
February 3, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29407232/t-cell-subsets-play-an-important-role-in-the-determination-of-the-clinical-outcome-of-helicobacter-pylori-infection
#5
REVIEW
Abdollah Jafarzadeh, Tiziana Larussa, Maryam Nemati, Shila Jalapour
Helicobacter pylori (H. pylori) is one of the most prevalent human pathogen and a persistent infection with this bacterium causes common pathologies, such as gastritis or peptic ulcers, and also less common but more serious pathologies, such as gastric cancer or gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The clinical outcome of gastrointestinal infection sustained by H. pylori is determined by the reciprocal interactions between virulence factors of the bacterium and host factors, including immune response genes...
January 30, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29375821/antigen-specific-treg-cells-in-immunological-tolerance-implications-for-allergic-diseases
#6
REVIEW
Azza Abdel-Gadir, Amir H Massoud, Talal A Chatila
Allergic diseases are chronic inflammatory disorders in which there is failure to mount effective tolerogenic immune responses to inciting allergens. The alarming rise in the prevalence of allergic diseases in recent decades has spurred investigations to elucidate the mechanisms of breakdown in tolerance in these disorders and means of restoring it. Tolerance to allergens is critically dependent on the generation of allergen-specific regulatory T (Treg) cells, which mediate a state of sustained non-responsiveness to the offending allergen...
2018: F1000Research
https://www.readbyqxmd.com/read/29375132/stimulation-of-tnf-receptor-type-2-expands-regulatory-t-cells-and-ameliorates-established-collagen-induced-arthritis-in-mice
#7
Vanessa Lamontain, Tobias Schmid, Dorothea Weber-Steffens, David Zeller, Zsuzsa Jenei-Lanzl, Harald Wajant, Rainer H Straub, Daniela N Männel
Tumor necrosis factor (TNF) and its receptors TNF receptor type 1 (TNFR1) and type 2 (TNFR2) have a central role in chronic inflammatory diseases. While TNFR1 mainly confers inflammation, activation of TNFR2 elicits not only pro-inflammatory but also anti-inflammatory effects. In this study, we wanted to investigate the anti-inflammatory therapeutic potential of selective activation of TNFR2 in mice with established collagen-induced arthritis. Mice with established arthritis induced by immunization with bovine collagen type II were treated with six injections of the TNFR2-specific agonist TNCscTNF80, given every second day...
January 29, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29367461/cd122-blockade-restores-immunological-tolerance-in-autoimmune-type-1-diabetes-via-multiple-mechanisms
#8
Xiaomei Yuan, Yi Dong, Naoya Tsurushita, J Yun Tso, Wenxian Fu
Signaling through IL-2/IL-15Rβ (CD122) is essential for the differentiation and function of T cells and NK cells. A mAb against CD122 has been implicated to suppress autoimmune type 1 diabetes (T1D) development in animal models. However, the mechanisms remain poorly understood. We find that in vivo administration of an anti-CD122 mAb (CD122 blockade) restores immune tolerance in nonobese diabetic (NOD) mice via multiple mechanisms. First, CD122 blockade selectively ablates pathogenic NK cells and memory phenotype CD8+ T cells from pancreatic islets...
January 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29365321/immune-rebound-associates-with-a-favorable-clinical-response-to-autologous-hsct-in-systemic-sclerosis-patients
#9
Lucas C M Arruda, Kelen C R Malmegrim, João R Lima-Júnior, Emmanuel Clave, Juliana B E Dias, Daniela A Moraes, Corinne Douay, Isabelle Fournier, Hélène Moins-Teisserenc, Antônio José Alberdi, Dimas T Covas, Belinda P Simões, Pauline Lansiaux, Antoine Toubert, Maria Carolina Oliveira
To evaluate the immunological mechanisms associated with clinical outcomes after autologous hematopoietic stem cell transplantation (AHSCT), focusing on regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic sclerosis (SSc) patients underwent simultaneous clinical and immunological evaluations over 36-month posttransplantation follow-up. Patients were retrospectively grouped into responders (n = 25) and nonresponders (n = 6), according to clinical response after AHSCT. Thymic function and B-cell neogenesis were respectively assessed by quantification of DNA excision circles generated during T- and B-cell receptor rearrangements...
January 23, 2018: Blood Advances
https://www.readbyqxmd.com/read/29349658/the-il-10-producing-regulatory-b-cells-b10-cells-and-regulatory-t-cell-subsets-in-neuromyelitis-optica-spectrum-disorder
#10
Eun Bin Cho, Hye-Jin Cho, Jin Myoung Seok, Ju-Hong Min, Eun-Suk Kang, Byoung Joon Kim
B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are certain B cells that suppress immune responses by producing regulatory cytokines, such as IL-10. In this study, we investigated the presence of IL-10-producing Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples) were enrolled. All NMOSD patients have received one or more immunosuppressive drugs...
January 19, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29327244/antibody-based-delivery-of-tumor-necrosis-factor-l19-tnf%C3%AE-and-interleukin-2-l19-il2-to-tumor-associated-blood-vessels-has-potent-immunological-and-anticancer-activity-in-the-syngeneic-j558l-balb-c-myeloma-model
#11
Hans D Menssen, Ulf Harnack, Ulrike Erben, Dario Neri, Burkhard Hirsch, Horst Dürkop
PURPOSE: To analyze the impact of TNFα or IL2 on human lymphocytes in vitro and the anti-tumor and immune-modifying effects of L19-IL2 and L19-TNFα on subcutaneously growing J558L myeloma in immunocompetent mice. METHODS: PBMCs from three healthy volunteers were incubated with IL2, TNFα, or with IL2 plus addition of TNFα (final 20 h). BALB/c J558L mice with subcutaneous tumors were treated with intravenous L19-TNFα plus L19-IL2, or controls. Tumor growth and intra- and peri-tumoral tissues were analyzed for micro-vessel density, necrosis, immune cell composition, and PD1 or PD-L1 expressing cells...
January 11, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29319881/systemic-il-2-anti-il-2ab-complex-combined-with-sublingual-immunotherapy-suppresses-experimental-food-allergy-in-mice-through-induction-of-mucosal-regulatory-t-cells
#12
Paola L Smaldini, Fernando Trejo, José L Cohen, Eliane Piaggio, Guillermo H Docena
Therapeutic tolerance restoration has been proven to modify food allergy in patients and animal models and although sublingual immunotherapy (SLIT) has showed promise, combined therapy may be necessary to achieve a strong and long-term tolerance. In this work, we combined SLIT with systemic administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL-2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediated experimental allergy. Balb/c mice were sensitized with cholera toxin and milk proteins and orally challenged with allergen to elicit hypersensitivity reactions...
January 10, 2018: Allergy
https://www.readbyqxmd.com/read/29315988/impaired-treg-and-nk-cells-profile-in-overweight-women-with-gestational-diabetes-mellitus
#13
Thalita Frutuoso Lobo, Camila de Moraes Borges, Rosiane Mattar, Caio Perez Gomes, Ana Geisa Santos de Angelo, Karen Priscilla Tezotto Pendeloski, Silvia Daher
PROBLEM: Maternal obesity is frequently associated with gestational diabetes mellitus (GDM), and immunological mechanisms seem to be involved in the physiopathology of these conditions. The aim of this study was to characterize the profile of immune cells in peripheral blood of overweight women with GDM. METHOD OF STUDY: This case-control study included 27 glucose-tolerant (controls) and 31 GDM overweight pregnant women. Flow cytometry was used to assess the number of regulatory T cells (Treg) and natural killer (NK) cells in the peripheral blood...
January 5, 2018: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/29301826/p53-reactive-t-cells-are-associated-with-clinical-benefit-in-patients-with-platinum-resistant-epithelial-ovarian-cancer-after-treatment-with-a-p53-vaccine-and-gemcitabine-chemotherapy
#14
Nicola R Hardwick, Paul Frankel, Christopher Ruel, Julie Kilpatrick, Weimin Tsai, Ferdynand Kos, Teodora I Kaltcheva, Lucille Leong, Robert Morgan, Vincent Chung, Raechelle Tinsley, Melissa Eng, Sharon P Wilczynski, Joshua D I Ellenhorn, Don J Diamond, Mihaela Cristea
PURPOSE: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29282311/a-cellular-microrna-facilitates-regulatory-t-lymphocyte-development-by-targeting-the-foxp3-promoter-tata-box-motif
#15
Yiwen Zhang, Weiwei Liu, Yingshi Chen, Jun Liu, Kang Wu, Lishi Su, Wanying Zhang, Yawen Jiang, Xu Zhang, Yijun Zhang, Chao Liu, Liang Tao, Bingfeng Liu, Hui Zhang
The CD4+CD25+FOXP3+ regulatory T cells (Tregs) mediate immunological self-tolerance and suppress various immune responses. FOXP3 is a key transcriptional factor for the generation and development of Tregs. Its expression is regulated by various cytokines including TGF-β, IL-2, and IL-10. It is important to further identify the regulatory factors for Tregs. Given that many microRNAs (miRNAs) could specifically interact with the core promoter region and specifically enhance the transcription of many target genes, we searched for any possible miRNA(s) targeting the core promoter region of the FOXP3 gene...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29281833/nlrp3-controls-the-development-of-gastrointestinal-cd11b-dendritic-cells-in-the-steady-state-and-during-chronic-bacterial-infection
#16
Isabelle C Arnold, Xiaozhou Zhang, Sabine Urban, Mariela Artola-Borán, Markus G Manz, Karen M Ottemann, Anne Müller
The gastric lamina propria is largely uncharted immunological territory. Here we describe the evolution and composition of the gastric, small intestinal, and colonic lamina propria mononuclear phagocyte system during the steady state and infection with the gastric pathogen Helicobacter pylori. We show that monocytes, CX3CR1hi macrophages, and CD11b+ dendritic cells are recruited to the infected stomach in a CCR2-dependent manner. All three populations, but not BATF3-dependent CD103+ DCs, sample red fluorescent protein (RFP)+Helicobacter pylori (H...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29259310/clinical-and-immunological-effects-of-rhil-2-therapy-in-eastern-chinese-patients-with-multidrug-resistant-tuberculosis
#17
Qi Tan, Rui Min, Guan-Qun Dai, Yan-Li Wang, Li Nan, Zhen Yang, Jun Xia, Shi-Yang Pan, Huang Mao, Wei-Ping Xie, Hong Wang
It is urgent to find an optimised therapy regimen for the control of MDR-TB globally. This study aimed to evaluate the efficiacy and safety of a combined regimen of rhIL-2 injection and standard chemotherapy within 18-month duration in a randomized controlled trial conducted in 14 centres in eastern China. From Jan. 2009 to July. 2016, 271 MDR-TB cases were enrolled and followed up in two groups, 142 cases in study group while 129 cases in control group. Clinical efficacy, safety and immune activity (Th1, Th17, Treg, IFN-γ, IL-17) among the two groups were evaluated and compared...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234980/low-dose-interleukin-2-as-a-modulator-of-treg-homeostasis-after-hsct-current-understanding-and-future-perspectives
#18
REVIEW
Ken-Ichi Matsuoka
CD4+CD25+Foxp3+ Treg is a functionally distinct subset of mature T cells with broad suppressive activity and has been shown to play an important role in the establishment of immune tolerance after HSCT. Altered cytokine environment in post-HSCT lymphopenia with a relative functional deficiency of IL-2 could hamper the reconstitution of Treg, leading to refractory GVHD. Based on the theory of low-dose IL-2 in which Treg can be selectively stimulated through the high-affinity IL-2 receptor, clinical studies have been conducted and demonstrated that low-dose IL-2 administration can restore Treg homeostasis and promote the expansion of this subset on the polymorphic processes of Treg reconstitution after HSCT...
December 12, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29234318/leprosy-as-a-complex-infection-breakdown-of-the-th1-and-th2-immune-paradigm-in-the-immunopathogenesis-of-the-disease
#19
REVIEW
Jorge Rodrigues de Sousa, Mirian Nacagami Sotto, Juarez Antonio Simões Quaresma
Leprosy is a chronic infectious disease whose evolution involves complex immune mechanisms of the host that influence the clinical presentation of the disease. For many years, the main interpretation of the host defense response was based on characterization of the established immune paradigm between T helper (Th) 1 and Th2 lymphocytes. However, with advances in the knowledge of immunology, new approaches have emerged along with the development of new immunological pathways that have changed the interpretation of the long-established paradigm of the polar forms of the disease, especially with the identification of new subtypes of T lymphocytes such as Th9, Th17, Th22, and Tregs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29229149/transfusion-of-ethylene-carbodiimide-fixed-donor-splenocytes-prolongs-survival-of-vascularized-skin-allografts
#20
Jianke Ding, Shiqiang Liu, Dongliang Zhang, Yajuan Song, Xianjie Ma, Chenggang Yi, Baoqiang Song, Bo Xiao, Yingjun Su, Shuzhong Guo
BACKGROUND: Allograft rejection is a major obstacle to the widespread clinical application of vascularized composite allotransplantation. Recent studies revealed a noncytoreductive strategy to protect allografts by the transfusion of ethylene carbodiimide-fixed donor splenocytes (ECDI-SPs). To determine whether this approach offers advantages in protecting skin allografts, we examined the immunological protection of infusing ECDI-SPs with a 30-d administration of rapamycin on the skin allografts of mice...
January 2018: Journal of Surgical Research
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