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Regulatory t cells

Ahmad Kotb, Antonina Klippert, Maria Daskalaki, Ulrike Sauermann, Christiane Stahl-Hennig, Berit Neumann
Granzyme B-expressing (GrB(+)) B cells are thought to contribute to immune dysfunctions in HIV patients, but so far their exact role is unknown. This report demonstrates for the first time the existence of GrB(+) B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, we found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. These frequencies correlated with plasma viral load and inversely with absolute CD4 T-cell counts...
October 25, 2016: Immunology and Cell Biology
Hee Yeon Won, Eun Sook Hwang
Regulatory T (Treg) cells with high expression of both CD25 and Foxp3 are developed in the thymus and also peripheral tissues. Treg cells suppress the activation and functions of effector T cells raised against specific antigens and are crucial for maintaining immune homeostasis. Treg cell development is associated with the induction of and epigenetic alterations of forkhead transcription factor Foxp3. Foxp3 expression is increased by the activation of several transcription factors including nuclear factor-kappa B (NF-κB), nuclear factor of activated T cells (NFAT), and Smad3 in response to various signals such as TGFβ, retinoic acid, and rapamycin...
October 25, 2016: Archives of Pharmacal Research
Viriya Kaewkangsadan, Chandan Verma, Jennifer M Eremin, Gerard Cowley, Mohammed Ilyas, Oleg Eremin
The tumour microenvironment consists of malignant cells, stroma, and immune cells. Prominent tumour-infiltrating lymphocytes (TILs) in breast cancer are associated with a good prognosis and are predictors of a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC). The contribution of different T effector/regulatory cells and cytokines to tumour cell death with NAC requires further characterisation and was investigated in this study. Breast tumours from 33 women with large and locally advanced breast cancers undergoing NAC were immunohistochemically (intratumoural, stromal) assessed for T cell subsets and cytokine expression using labelled antibodies, employing established semiquantitative methods...
2016: Journal of Immunology Research
Yong-Chao Qiao, Jian Shen, Lan He, Xue-Zhi Hong, Fang Tian, Yan-Hong Pan, Ling Liang, Xiao-Xi Zhang, Hai-Lu Zhao
Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β (TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM). Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-α in T2DM patients versus healthy controls. Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis...
2016: Journal of Diabetes Research
Sasha E Stanton, Mary L Disis
Tumor infiltrating lymphocytes (TIL) play an essential role in mediating response to chemotherapy and improving clinical outcomes in all subtypes of breast cancer. Triple negative breast cancers (TN) are most likely to have tumors with >50 % lymphocytic infiltrate, termed lymphocyte predominant breast cancer, and derive the greatest survival benefit from each 10 % increase in TIL. The majority of HER2(+) breast cancers have similar level of immune infiltrate as TN breast cancer yet the presence of TILs has not shown the same survival benefit...
2016: Journal for Immunotherapy of Cancer
Neha Kamran, Mayuri Chandran, Pedro R Lowenstein, Maria G Castro
Various preclinical studies have demonstrated that the success of immunotherapeutic strategies in inhibiting tumor progression in animal models of Glioblastoma multiforme (GBM). It is also evident that tumor-induced immune suppression drastically impacts the efficacy of immune based therapies. Among the mechanisms employed by GBM to induce immunosuppression is the accumulation of regulatory T cells (Tregs) and Myeloid derived suppressor cells (MDSCs). Advancing our understanding about the pathways regulating the expansion, accumulation and activity of MDSCs will allow for the development of therapies aimed at abolishing the inhibitory effect of these cells on immunotherapeutic approaches...
October 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Kristian Tonby, Ida Wergeland, Nora V Lieske, Dag Kvale, Kjetil Tasken, Anne M Dyrhol-Riise
BACKGROUND: Tuberculosis (TB) causes a major burden on global health with long and cumbersome TB treatment regimens. Host-directed immune modulating therapies have been suggested as adjunctive treatment to TB antibiotics. Upregulated cyclooxygenase-2 (COX-2)-prostaglandin E2 (PGE2) signaling pathway may cause a dysfunctional immune response that favors survival and replication of Mycobacterium tuberculosis (Mtb). METHODS: Blood samples were obtained from patients with latent TB (n = 9) and active TB (n = 33) before initiation of anti-TB chemotherapy...
October 24, 2016: BMC Infectious Diseases
Jennie Johnstone, Robin Parsons, Fernando Botelho, Jamie Millar, Shelly McNeil, Tamas Fulop, Janet E McElhaney, Melissa K Andrew, Stephen D Walter, P J Devereaux, Mehrnoush Malek, Ryan R Brinkman, Jonathan Bramson, Mark Loeb
OBJECTIVES: To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents. DESIGN: Cross sectional study of frailty; prospective cohort study of mortality. SETTING: Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011. PARTICIPANTS: Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female)...
October 24, 2016: Journal of the American Geriatrics Society
Kyle J Seamon, Namandje N Bumpus, James T Stivers
Sterile Alpha Motif and HD Domain Protein 1 (SAMHD1) is a unique enzyme that has important roles in nucleic acid metabolism, viral restriction, and the pathogenesis of autoimmune diseases and cancer. Although much attention has been focused on its dNTP triphosphohydrolase activity in viral restriction and disease, SAMHD1 also binds to single-stranded RNA and DNA. Here we utilize a UV crosslinking method using 5-bromodeoxyuridine-substituted oligonucleotides coupled with high-resolution mass spectrometry (HRMS) to identify the binding site for single-stranded nucleic acids (ssNA) on SAMHD1...
October 24, 2016: Biochemistry
Lei Wang, Na Peng, Xiaoyan Hu, Wentao Liang, Kai Liang, Guizhu Peng
Objective To evaluate the effects of cryopreservation on the proliferation and killing activity of lymphocytes, and explore a novel protocol of preparing autologous mouse cytotoxic T lymphocytes (CTLs). Methods Mononuclear cells derived from spleen (5.0×10(6)/mL) were cryopreserved in CELLBANKER2 for 6 days and recovered in water bath at 39DegreesCelsius. The fresh lymphocytes and post-cryopreservation lymphocytes were induced by CD3 mAb (100 ng/mL) and recombinant mouse interleukin 2 (rmIL-2, 100 ng/mL) to obtain cytokine-induced killer cells (CIKs)...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Anke Theil, Carmen Wilhelm, Matthias Kuhn, Andreas Petzold, Sebastian Tuve, Uta Oelschlägel, Andreas Dahl, Martin Bornhäuser, Ezio Bonifacio, Anne Eugster
T regulatory cell (Treg) therapy has been exploited in autoimmune disease, solid organ transplantation and in efforts to prevent or treat graft-versus-host disease (GvHD). However, our knowledge on in vivo persistence of transfused Treg is limited. Whether Treg transfusion leads to notable changes in the overall Treg repertoire and or whether longevity of Treg in the periphery is restricted to certain clones is unknown. Here we use T cell receptor alpha chain sequencing (TCRα-NGS) to monitor changes in the repertoire of Treg upon polyclonal expansion and after subsequent adoptive transfer...
October 24, 2016: Clinical and Experimental Immunology
Wei Du, Nicholas D Leigh, Guanglin Bian, Emad Alqassim, Rachel E O'Neill, Lin Mei, Jingxin Qiu, Hong Liu, Philip L McCarthy, Xuefang Cao
Granzyme B (GzmB) is a key cytotoxic molecule utilized by T cells to kill pathogen-infected cells or transformed tumor cells. Previous studies using allogeneic hematopoietic cell transplantation (allo-HCT) murine models showed that GzmB is required for CD8(+) T cells to cause graft-versus-host disease (GVHD). However, our recent study demonstrated that GzmB-mediated damage of CD8(+) T cells diminished their graft-versus-tumor (GVT) activity. In this study, we examined the role of GzmB in GVT effect mediated by conventional CD4(+)CD25(-) T cells (CD4(+) Tcon)...
2016: J Immunol Res Ther
Adriaan A van Beek, Bruno Sovran, Floor Hugenholtz, Ben Meijer, Joanne A Hoogerland, Violeta Mihailova, Corine van der Ploeg, Clara Belzer, Mark V Boekschoten, Jan H J Hoeijmakers, Wilbert P Vermeij, Paul de Vos, Jerry M Wells, Pieter J M Leenen, Claudio Nicoletti, Rudi W Hendriks, Huub F J Savelkoul
Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1(-/Δ7) mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1(-/Δ7) mice was characterized by a thin (< 10 μm) mucus layer...
2016: Frontiers in Immunology
Sawinee Aupanun, Patchara Phuektes, Saranya Poapolathep, Samak Sutjarit, Mario Giorgi, Amnart Poapolathep
Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, along with deoxynivalenol (DON) and nivalenol (NIV) as a contaminant in cereals. Our previous study demonstrated that a 14-day FX exposure caused apoptosis in the lymphoid tissues of mice, especially at 0.5 mg/kg bodyweight. However, the relationship between low concentrations of FX and apoptotic molecular machinery remains unclear. In the present study, we investigated the genetic regulatory mechanisms in the thymus and Peyer's patches of mice after 14 days oral administration of FX at 0...
October 20, 2016: Toxicon: Official Journal of the International Society on Toxinology
Carlos A Aguilar, Ramona Pop, Anna Shcherbina, Alain Watts, Ronald W Matheny, Davide Cacchiarelli, Woojin M Han, Eunjung Shin, Shadi A Nakhai, Young C Jang, Christopher T Carrigan, Casey A Gifford, Melissa A Kottke, Marcella Cesana, Jackson Lee, Maria L Urso, Alexander Meissner
Following injury, adult skeletal muscle undergoes a well-coordinated sequence of molecular and physiological events to promote repair and regeneration. However, a thorough understanding of the in vivo epigenomic and transcriptional mechanisms that control these reparative events is lacking. To address this, we monitored the in vivo dynamics of three histone modifications and coding and noncoding RNA expression throughout the regenerative process in a mouse model of traumatic muscle injury. We first illustrate how both coding and noncoding RNAs in tissues and sorted satellite cells are modified and regulated during various stages after trauma...
October 20, 2016: Stem Cell Reports
J Budna, Ł Spychalski, M Kaczmarek, M Frydrychowicz, J Goździk-Spychalska, H Batura-Gabryel, J Sikora
Tumors exert suppressive effects on the host immune system and tumor progression can be linked to functional impairments of immune cells. Regulatory T cells (Treg) are a subpopulation of T lymphocytes and play a key role in suppressing immune responses against autoimmune diseases and cancer. The aim of the study was to investigate the prevalence of Treg in malignant and benign pleural effusions and to evaluate the relationship between Treg frequency and disease advance. Pleural effusions from 76 patients were subjected to a routine laboratory diagnosis and analyzed by conventional cytology...
October 18, 2016: Immunobiology
Petra Bacher, Frederik Heinrich, Ulrik Stervbo, Mikalai Nienen, Marco Vahldieck, Christina Iwert, Katrin Vogt, Jutta Kollet, Nina Babel, Birgit Sawitzki, Carsten Schwarz, Stefan Bereswill, Markus M Heimesaat, Guido Heine, Gabriele Gadermaier, Claudia Asam, Mario Assenmacher, Olaf Kniemeyer, Axel A Brakhage, Fátima Ferreira, Michael Wallner, Margitta Worm, Alexander Scheffold
FOXP3+ regulatory T cells (Tregs) maintain tolerance against self-antigens and innocuous environmental antigens. However, it is still unknown whether Treg-mediated tolerance is antigen specific and how Treg specificity contributes to the selective loss of tolerance, as observed in human immunopathologies such as allergies. Here, we used antigen-reactive T cell enrichment to identify antigen-specific human Tregs. We demonstrate dominant Treg-mediated tolerance against particulate aeroallergens, such as pollen, house dust mites, and fungal spores...
October 18, 2016: Cell
J Fotschki, A M Szyc, J M Laparra, L H Markiewicz, B Wróblewska
The aim of this study was to examine immune adaptive changes, the expression of innate biomarkers and variations in intestinal microbiota composition after horse-milk administration in BALB/c mice, which were sensitized intraperitoneally using cow β-lactoglobulin and α-casein with aluminum adjuvant. We measured serum antibody IgE levels and the expression of MCP-1, IL-4, and TNF-α in duodenal samples. Changes in immune cell populations in peripheral blood were quantified using flow cytometry, and intestinal microbiota composition was assessed using real-time PCR...
October 19, 2016: Journal of Dairy Science
Shanzheng Lu, Ganggang Shi, Xiaoxi Xu, Grace Wang, Xu Lan, Peng Sun, Xiang Li, Baoren Zhang, Xiangying Gu, Thomas E Ichim, Hao Wang
BACKGROUND: The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI). METHODS: An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4...
October 22, 2016: Journal of Translational Medicine
Flore Amat, Pauline Tallon, Anne-Perrine Foray, Bénédicte Michaud, Nathalie Lambert, Philippe Saint-Pierre, Lucienne Chatenoud, Jocelyne Just
Allergic asthma is an inflammatory disease of the airways, resulting from an inappropriate immune response to inhaled allergens, which involves multiple inflammatory cells and mediators that contribute to airway hyper-responsiveness. Omalizumab is a monoclonal antibody, specifically directed to the C-Epsilon3 domain of immunoglobulin E (IgE), indicated as an additional therapy in severe allergic asthma [1]. Impaired function of regulatory T cells (Treg) is incriminated in the aberrant asthma inflammatory response [2]...
October 22, 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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