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M Burgess, S Mapp, R Mazzieri, C Cheung, L Chambers, S R Mattarollo, P Mollee, D Gill, N A Saunders
Resistance to therapeutic antibodies in chronic lymphocytic leukaemia (CLL) is common. In this study, we show that therapeutic antibodies against CD62L (CD62L-Ab) or CD20 (obinutuzumab) were able to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADP) in primary cultures of CLL cells. CLL cells derived from patients with active disease requiring treatment displayed resistance to these antibodies, whereas patients with stable disease were sensitive. Using enrichment strategies and transcriptomic analyses, we show that antibody-dependent tumour cell killing was FcγR-dependent and mediated by macrophages...
October 17, 2016: Oncogene
Diana M Giraldo, Juan C Hernandez, Silvio Urcuqui-Inchima
Neutrophils are key effector cells of the innate immune system and are involved in the host defense against invading pathogens such as viruses. Recently, it was reported that HIV-1-neutrophil interaction triggers neutrophil activation and promotes expression of Toll-like receptors (TLRs). Here, we assessed the role of single-stranded RNA40 (ssRNA40) derived from HIV-1 in neutrophil activation. We observed functional activation of neutrophils in response to HIV-1-derived ssRNA40 based on the expression of TLR7/8, RIG-I, and MDA5, induction of cytokines (IL-6 and TNF-α), and the production of reactive oxygen species (ROS)...
October 7, 2016: Immunologic Research
Ronald Schilderink, Matthew Bell, Eleonora Reginato, Chris Patten, Inmaculada Rioja, Francisca W Hilbers, Pawel A Kabala, Kris A Reedquist, David F Tough, Paul Peter Tak, Rab K Prinjha, Wouter J de Jonge
Transcription of inflammatory genes is tightly regulated by acetylation and deacetylation of histone tails. An inhibitor of the acetylated-lysine reader bromodomain and extra-terminal domain (BET) proteins, I-BET151, is known to counteract the induction of expression of inflammatory genes in macrophages. We have investigated the effects of I-BET151 on dendritic cell function, including expression of co-stimulatory molecules and cytokines, and capacity for T cell activation. Treatment of mouse bone marrow derived dendritic cells (BMDC) and human monocyte derived DCs (mdDC) with I-BET151 reduced LPS-induced expression of co-stimulatory molecules, as well as the production of multiple cyokines and chemokines...
October 3, 2016: Molecular Immunology
Esin Aktas Cetin, Leyla Pur Ozyigit, Yusuf Metin Gelmez, Erkan Cakir, Ahmet Hakan Gedik, Gunnur Deniz
OBJECTIVES: Childhood tuberculosis (TB) comprises an important part of the world's TB burden. Monocytes set up the early phase of infection because of innate immune responses. Understanding the changes in monocyte subsets during multisystem infectious diseases may be important for the development of novel diagnostic and therapeutic strategies. The aim of this study was to evaluate the monocyte phenotype together with the cytokine secretion profiles of children with pulmonary tuberculosis...
September 29, 2016: Pediatric Pulmonology
Andrew Baird, Chenliang Deng, Matthew H Eliceiri, Fatima Haghi, Xitong Dang, Raul Coimbra, Todd W Costantini, Bruce E Torbett, Brian P Eliceiri
Mice engrafted with human CD34(+) hematopoietic stem and progenitor cells (CD34(+) -HSPCs) have been used to study human infection, diabetes, sepsis, and burn, suggesting that they could be highly amenable to characterizing the human inflammatory response to injury. To this end, human leukocytes infiltrating subcutaneous implants of polyvinyl alcohol (PVA) sponges were analyzed in immunodeficient NSG mice reconstituted with CD34(+) -HSPCs. It was reported that human CD45(+) (hCD45(+) ) leukocytes were present in PVA sponges 3 and 7 days postimplantation and could be localized within the sponges by immunohistochemistry...
September 24, 2016: Wound Repair and Regeneration
Yao-Shen Chen, Hsi-Hsun Lin, Pei-Tan Hsueh, Wei-Fan Ni, Pei-Ju Liu, Pei-Shih Chen, Hsin-Hou Chang, Der-Shan Sun, Ya-Lei Chen
The development of neurologic melioidosis was linked to the elicitation of Burkholderia pseudomallei-infected L-selectin(hi)CD11b(+) BALB/c cells in our previous study. However, whether monocytic L-selectin (CD62L, encoded by the sell gene) is a key factor remains uncertain. In the present study, after establishing multi-organ foci via hematogenous routes, we demonstrated that B. pseudomallei GFP steadily persisted in blood, splenic, hepatic and bone marrow (BM) Ly6C monocytes; however, the circulating CD16/32(+)CD45(hi)GFP(+) brain-infiltrating leukocytes (BILs) derived from the blood Ly6C monocytes were expanded in BALB/c but not in C57BL/6 bacteremic melioidosis...
September 19, 2016: Virulence
Karsten Mahnke, Jurgina Useliene, Sabine Ring, Paula Kage, Verena Jendrossek, Simon C Robson, Matilda Bylaite-Bucinskiene, Kerstin Steinbrink, Alexander H Enk
Injection of regulatory T cells (Treg) followed by sensitization with TNCB induced a transient increase in size and cellularity of skin draining lymph nodes (LN) in mice. This led us to hypothesize that Treg may affect the trafficking of T cells from - and to peripheral LN. Two to three hours after sensitization we found fewer CD8(+) T cells expressing CD62L in LN as compared to untreated controls. Injection of wildtype Treg prevented this down-regulation of CD62L. In contrast, Treg devoid of the ATP-degrading ecto-enzyme CD39 were unable to do so...
September 10, 2016: Journal of Investigative Dermatology
Jiali Zhang, Jing Xu, Rong-Xin Zhang, Yi Zhang, Qing-Jian Ou, Jin-Qing Li, Ze-Zhou Jiang, Xiao-Jun Wu, Yu-Jing Fang, Limin Zheng
PURPOSE: CD169 was first identified on macrophages (Mϕ) and linked to antigen presentation. Here, we showed CD169 expression on some CD8(+) T lymphocytes in regional lymph nodes (LNs) and investigated the function and clinical relevance of CD169(+)CD8(+) T cells in tumor-draining LNs of colorectal cancer (CRC) patients. EXPERIMENTAL DESIGN: Fresh tumor-draining LN tissues from 39 randomly enrolled patients were assessed by flow cytometry for activation and differentiation of CD169(+)CD8(+) T cells and T cell-mediated killing of tumor cells...
July 2016: Oncoimmunology
Peder S Olofsson, Benjamin E Steinberg, Roozbeh Sobbi, Maureen A Cox, Mohamed N Ahmed, Michaela Oswald, Ferenc Szekeres, William M Hanes, Andrea Introini, Shu Fang Liu, Nichol E Holodick, Thomas L Rothstein, Cecilia Lövdahl, Sangeeta S Chavan, Huan Yang, Valentin A Pavlov, Kristina Broliden, Ulf Andersson, Betty Diamond, Edmund J Miller, Anders Arner, Peter K Gregersen, Peter H Backx, Tak W Mak, Kevin J Tracey
Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been determined. We previously showed that CD4(+) T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals. Here we show that these CD4(+)CD44(hi)CD62L(lo) T helper cells by gene expression are a distinct T-cell population defined by ChAT (CD4 TChAT). Mice lacking ChAT expression in CD4(+) cells have elevated arterial blood pressure, compared to littermate controls...
October 2016: Nature Biotechnology
Carin Wallquist, Ladan Mansouri, Mattias Norrbäck, Britta Hylander, Stefan H Jacobson, Joachim Lundahl
BACKGROUND: Despite the absence of clinical symptoms, patients with chronic kidney disease (CKD) exhibit elevated levels of pro-inflammatory markers. To investigate whether it is possible to detect inflammatory activity and altered monocyte function at an early stage of renal disease, we studied patients with CKD stages 2-3 over 5 years. METHODS: The expression of adhesion molecules on monocytes at resting state and after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP), as well as oxidative metabolism capacity was measured with flow cytometry in 108 CKD patients and healthy controls...
September 8, 2016: American Journal of Nephrology
Zhihong Chen, Jue Pan, Yi Jia, Dandan Li, Zhihui Min, Xiaoqiong Su, Honglei Yuan, Geng Shen, Shengxuan Cao, Lei Zhu, Xiangdong Wang
BACKGROUND: Recent data have demonstrated that long-lived memory T cells are present in the human lung and can play significant roles in the pathogenesis of specific allergic and autoimmune diseases. However, most evidence has been obtained from mouse studies, and the potential roles of memory T cells in human allergic diseases, such as asthma, remain largely unknown. METHODS: Thirty-three asthmatics, 26 chronic obstructive pulmonary disease (COPD) patients, and 22 healthy volunteers were enrolled in this study...
August 31, 2016: Cell Biology and Toxicology
Kalahe Hewage Iresha Nadeeka Madushani Herath, So Jin Bing, Jinhee Cho, Areum Kim, Sumin Shin, Gi-Ok Kim, Jong-Chul Lee, Youngheun Jee
Dangyuja (Citrus grandis Osbeck), a citrus cultivated in southern Korea, has been used in traditional medicine for its anti-inflammatory effect. In this study, we investigated the anti-inflammatory potential of extract of Citrus grandis Osbeck (ECGO). In in vitro assays, ECGO treatment of concanavalin A (10μg/ml, for 24h) stimulated splenocytes showed significant reduction in CD44/CD62L(+) T cell population and a marked decrease in the production of inflammatory cytokines IL-2, IFN-γ and IL-4. Interestingly, in vivo assays of ECGO topical treatment (100μg/20μl/ear) significantly mitigated the TPA (4μg/20μl/ear) induced edema induction and Myeloperoxidase activity...
August 27, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
(no author information available yet)
No abstract text is available yet for this article.
August 30, 2016: Neurology
Nicholas Schwab, Tilman Schneider-Hohendorf, Heinz Wiendl, Ellen Cahir-McFarland, Richard M Ransohoff, Linda Lieberman, Tatiana Plavina
No abstract text is available yet for this article.
August 30, 2016: Neurology
Christoph Priesner, Krasimira Aleksandrova, Ruth Esser, Nadine Mockel-Tenbrinck, Jana Leise, Katharina Drechsel, Michael Marburger, Andrea Quaiser, Lilia Goudeva, Lubomir Arseniev, Andrew Kaiser, Wolfgang Glienke, Ulrike Koehl
Multiple clinical studies demonstrated that adaptive immunotherapy using redirected T cells against advanced cancer has led to promising results with improved survival of the patients. The continuously increasing interest in those advanced Gene Therapy Medicinal Products (GTMPs) leads to a challenge on the manufacturing side regarding automation, process robustness and cell storage. Therefore, our study addresses the proof of principle in clinical-scale selection, stimulation, transduction and expansion of T cells using the automated closed CliniMACS® Prodigy system...
August 25, 2016: Human Gene Therapy
Vanessa Sue Wacleche, Jean-Philippe Goulet, Annie Gosselin, Patricia Monteiro, Hugo Soudeyns, Rémi Fromentin, Mohammad-Ali Jenabian, Shant Vartanian, Steven G Deeks, Nicolas Chomont, Jean-Pierre Routy, Petronela Ancuta
BACKGROUND: Th17 cells are permissive to HIV-1 infection and their depletion from the gut of infected individuals leads to microbial translocation, a major cause for non-AIDS co-morbidities. Most recent evidence supports the contribution of long-lived Th17 cells to HIV persistence during antiretroviral therapy (ART). However, the identity of long-lived Th17 cells remains unknown. RESULTS: Here, we performed an in-depth transcriptional and functional characterization of four distinct Th17 subsets and investigated their contribution to HIV reservoir persistence during ART...
2016: Retrovirology
Claire Mesnil, Stéfanie Raulier, Geneviève Paulissen, Xue Xiao, Mark A Birrell, Dimitri Pirottin, Thibaut Janss, Philipp Starkl, Eve Ramery, Monique Henket, Florence N Schleich, Marc Radermecker, Kris Thielemans, Laurent Gillet, Marc Thiry, Maria G Belvisi, Renaud Louis, Christophe Desmet, Thomas Marichal, Fabrice Bureau
Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus...
September 1, 2016: Journal of Clinical Investigation
Kajsa E Prokopec, Anna-Maria Georgoudaki, Silke Sohn, Fredrik Wermeling, Hans Grönlund, Emma Lindh, Michael C Carroll, Mikael C I Karlsson
Marginal zone macrophages (MZM) are strategically located in the spleen, lining the marginal sinus where they sense inflammation and capture Ag from the circulation. One of the receptors expressed by MZM is scavenger receptor macrophage receptor with collagenous structure (MARCO), which has affinity for modified self-antigens. In this article, we show that engagement of MARCO on murine macrophages induces extracellular ATP and loss of CD21 and CD62L on marginal zone B cells. Engagement of MARCO also leads to reduction of Ag transport by marginal zone B cells and affects the subsequent immune response...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jiangping Li, Sifei Yu, Yannan Zhang, Juan Shen, Suihua Lao, Baiqing Li, Binyan Yang, Changyou Wu
Control of infection with Mycobacterium tuberculosis (M.tb) requires effective antigen-specific immune response, including CD4(+) and CD8(+) T-cell responses; however, the local immune response of mucosal-associated invariant T (MAIT) cells at the site of infection is unclear. MAIT cells are a prevalent and unique, innate T-cell population that expresses the semi-invariant T-cell receptor TCRVα7.2. Our direct ex vivo analysis demonstrates that the frequency of MAIT cells in pleural fluid was much higher than that in peripheral blood from healthy donors, but much lower than that in peripheral blood from patients with tuberculosis...
August 9, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
I V Kudryavtsev, M K Serebryakova, A A Totolyan
The study was carried out to develop standard indicators of relative and absolute content of main populations of T-helpers in peripheral blood of conditionally healthy donors. The examination was implemented to sampling of 52 healthy individuals (29 males and 23 females) aged 18-65 years (median is 30 years). The multicolor cytofluorimetric analysis was applied using panel of following antibodies: CD45RA-FITC, CD62L-PE, CCR4-PerCP/Cy5.5; CCR6-PE/Cy7, CXCR3-APC, CD3-APC-AF750, CD4-Pacific Blue and CXCR5-Brilliant Violet 510TM...
March 2016: Klinicheskaia Laboratornaia Diagnostika
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