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https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#1
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28087948/regulation-of-immunity-to-tuberculosis
#2
Susanna Brighenti, Diane J Ordway
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087940/the-memory-immune-response-to-tuberculosis
#3
Joanna R Kirman, Marcela I Henao-Tamayo, Else Marie Agger
Immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses to Mycobacterium tuberculosis will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087939/dendritic-cells-in-the-immune-system-history-lineages-tissues-tolerance-and-immunity
#4
Jonathan M Austyn
The aim of this review is to provide a coherent framework for understanding dendritic cells (DCs). It has seven sections. The introduction provides an overview of the immune system and essential concepts, particularly for the nonspecialist reader. Next, the "History" section outlines the early evolution of ideas about DCs and highlights some sources of confusion that still exist today. The "Lineages" section then focuses on five different populations of DCs: two subsets of "classical" DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087817/t-cell-redeployment-and-intracellular-cytokine-expression-following-exercise-effects-of-exercise-intensity-and-cytomegalovirus-infection
#5
Emily C LaVoy, Maryam Hussain, Justin Reed, Hawley Kunz, Mira Pistillo, Austin B Bigley, Richard J Simpson
The magnitude of lymphocytosis following exercise is directly related to exercise intensity. Infection with cytomegalovirus (CMV) also augments lymphocytosis after exercise. It is not known if the enhanced T-cell response to exercise due to CMV depends on exercise intensity. Furthermore, exercise-induced changes in T-cell expression of type I and type II cytokines are thought to be intensity dependent, but direct comparisons are lacking. The aim of this experiment was to determine if CMV affects the exercise-induced redistribution of T-cell subsets at varying intensities, and determine the effect of exercise intensity on CD8(+) T-cell cytokine expression...
January 2017: Physiological Reports
https://www.readbyqxmd.com/read/28087740/bone-microenvironment-changes-in-latexin-expression-promote-chemoresistance
#6
Mi Zhang, Mary Osisami, Jinlu Dai, Jill M Keller, June Escara-Wilke, Atsushi Mizokami, Evan T Keller
: Although docetaxel (DOX) is the standard of care for advanced prostate cancer (PCa), most patients develop resistance to DOX. Therefore, elucidating the mechanism that underlies resistance to DOX is critical to enhance therapeutic intervention. Mining cDNA microarray from the PC-3 PCa cell line and its DOX-resistant derivative (PC3-TxR) revealed decreased latexin (LXN) expression in the resistant cells. LXN expression was inversely correlated with taxane resistance in a panel of PCa cell lines...
January 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28087712/pdx1-dynamically-regulates-pancreatic-ductal-adenocarcinoma-initiation-and-maintenance
#7
Nilotpal Roy, Kenneth K Takeuchi, Jeanine M Ruggeri, Peter Bailey, David Chang, Joey Li, Laura Leonhardt, Sapna Puri, Megan T Hoffman, Shan Gao, Christopher J Halbrook, Yan Song, Mats Ljungman, Shivani Malik, Christopher V E Wright, David W Dawson, Andrew V Biankin, Matthias Hebrok, Howard C Crawford
Aberrant activation of embryonic signaling pathways is frequent in pancreatic ductal adenocarcinoma (PDA), making developmental regulators therapeutically attractive. Here we demonstrate diverse functions for pancreatic and duodenal homeobox 1 (PDX1), a transcription factor indispensable for pancreas development, in the progression from normal exocrine cells to metastatic PDA. We identify a critical role for PDX1 in maintaining acinar cell identity, thus resisting the formation of pancreatic intraepithelial neoplasia (PanIN)-derived PDA...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28087671/induction-and-differentiation-of-il-10-producing-regulatory-b-cells-from-healthy-blood-donors-and-rheumatoid-arthritis-patients
#8
Zsuzsanna Bankó, Judit Pozsgay, Dániel Szili, Mária Tóth, Tamás Gáti, György Nagy, Bernadette Rojkovich, Gabriella Sármay
The most important feature of B cells is the production of Abs upon activation; additionally, B cells produce pro- and anti-inflammatory cytokines in response to certain stimuli. IL-10-producing B cells represent a major subset of regulatory B cells (Bregs) that suppress autoimmune and inflammatory responses. B cells play a crucial role in the development and maintenance of the chronic inflammatory autoimmune disease rheumatoid arthritis (RA); however, controversial data are available on IL-10- producing Bregs in RA...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087664/human-blood-cd1c-dendritic-cells-encompass-cd5high-and-cd5low-subsets-that-differ-significantly-in-phenotype-gene-expression-and-functions
#9
Xiangyun Yin, Haisheng Yu, Xiaoyang Jin, Jingyun Li, Hao Guo, Quanxing Shi, Zhao Yin, Yong Xu, Xuefei Wang, Rong Liu, Shouli Wang, Liguo Zhang
There are three major dendritic cell (DC) subsets in both humans and mice, that is, plasmacytoid DCs and two types of conventional DCs (cDCs), cDC1s and cDC2s. cDC2s are important for polarizing CD4(+) naive T cells into different subsets, including Th1, Th2, Th17, Th22, and regulatory T cells. In mice, cDC2s can be further divided into phenotypically and functionally distinct subgroups. However, subsets of human cDC2s have not been reported. In the present study, we showed that human blood CD1c(+) cDCs (cDC2s) can be further separated into two subpopulations according to their CD5 expression status...
January 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28087652/differential-regulation-of-cd103-%C3%AE-e-integrin-expression-in-human-dendritic-cells-by-retinoic-acid-and-toll-like-receptor-ligands
#10
Mandi M Roe, Steve Swain, T Andrew Sebrell, Marisa A Sewell, Madison M Collins, Brian A Perrino, Phillip D Smith, Lesley E Smythies, Diane Bimczok
CD103 (αE integrin) is an important dendritic cell (DC) marker that characterizes functionally distinct DC subsets in mice and humans. However, the mechanism by which CD103 expression is regulated in human DCs and the role of CD103 for DC function are not very well understood. Here, we show that retinoic acid (RA) treatment of human monocyte-derived DCs (MoDCs) increased the ability of the DCs to synthesize RA and induced MoDC expression of CD103 and β7 at the mRNA and protein level. In contrast, RA was unable to induce the expression of CD103 in primary human DCs isolated from the gastric mucosa...
January 13, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28087292/loss-of-cd28-within-cd4-t-cell-subsets-from-cervical-cancer-patients-is-accompanied-by-the-acquisition-of-intracellular-perforin-and-is-further-enhanced-by-nkg2d-expression
#11
Marta Escarra-Senmarti, Miriam Ruth Bueno-Topete, Luis Felipe Jave-Suarez, Eduardo Gomez-Bañuelos, Jorge Gutierrez-Franco, Natali Vega-Magaña, Adriana Aguilar-Lemarroy, Ana Laura Pereira-Suarez, Jesse Haramati, Susana Del Toro-Arreola
CD28 is well characterized as an essential co-stimulatory receptor critical for activation, proliferation and survival processes in CD4(+) T cells. Populations of CD4(+)CD28(null) T cells, with apparently contradictory physiological roles, have recently been reported, along with the co-expression of the NK activating receptor NKG2D, in autoimmune diseases and chronic viral inflammation. Paradoxically, studies in cancer suggest that an expanded CD4(+)NKG2D(+) population may be armed with immunosuppressive properties...
January 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28087077/alteration-of-cd39-foxp3-cd4-t-cell-and-cytokine-levels-in-eae-ms-following-anti-cd52-treatment
#12
Anudeep B Pant, Yan Wang, Daniel W Mielcarz, Eli J Kasper, Kiel M Telesford, Megan Mishra, Azizul Haque, Jacqueline Smith, Lloyd H Kasper, Sakhina Begum-Haque
While examining the therapeutic value of anti-CD52 antibody against EAE/MS, we identified a unique subset of CD39+ Tregs in repopulating GALT tissues, a major lymphoid reservoir, which was accompanied by amelioration of disease. Furthermore, anti-CD52 treatment leads to increased expression of BDNF, IL-10, and SMAD3 in the brains of EAE mice. This condition is associated with suppression of IL-17, a critical inflammatory factor in EAE/MS progression. Additionally, we found elevated levels of CD4+CD39+ Tregs in PBMCs of RRMS patients treated with humanized anti-CD52 mAb...
December 21, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28086758/toxoplasmosis-associated-iris-involving-the-cns-a-case-report-with-longitudinal-analysis-of-t-cell-subsets
#13
Rita Rb-Silva, Claudia Nobrega, Eugénia Reiriz, Soraia Almeida, Rui Sarmento-Castro, Margarida Correia-Neves, Ana Horta
BACKGROUND: HIV-infected patients may present an unforeseen clinical worsening after initiating antiretroviral therapy known as immune reconstitution inflammatory syndrome (IRIS). This syndrome is characterized by a heightened inflammatory response toward infectious or non-infectious triggers, and it may affect different organs. Diagnosis of IRIS involving the central nervous system (CNS-IRIS) is challenging due to heterogeneous manifestations, absence of biomarkers to identify this condition, risk of long-term sequelae and high mortality...
January 13, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28081442/mapping-and-role-of-the-cd8-t-cell-response-during-primary-zika-virus-infection-in-mice
#14
Annie Elong Ngono, Edward A Vizcarra, William W Tang, Nicholas Sheets, Yunichel Joo, Kenneth Kim, Matthew J Gorman, Michael S Diamond, Sujan Shresta
CD8(+) T cells may play a dual role in protection against and pathogenesis of flaviviruses, including Zika virus (ZIKV). We evaluated the CD8(+) T cell response in ZIKV-infected LysMCre(+)IFNAR(fl/fl) C57BL/6 (H-2(b)) mice lacking the type I interferon receptor in a subset of myeloid cells. In total, 26 and 15 CD8(+) T cell-reactive peptides for ZIKV African (MR766) and Asian (FSS13025) lineage strains, respectively, were identified and validated. CD8(+) T cells from infected mice were polyfunctional and mediated cytotoxicity...
January 11, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28081241/cd25-cd127-foxp3-cells-represent-a-major-subpopulation-of-cd8-t-cells-in-the-eye-chambers-of-normal-mice
#15
Tomasz Maślanka, Natalia Ziółkowska, Hubert Ziółkowski, Joanna Małaczewska
The aim of this study has been to determine whether eye chambers constitute part of the normal migratory pathway of naive CD4+ and CD8+ T cells in mouse and if natural CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+ regulatory T cells are present within these eye compartments. To this aim, the cells obtained from aqueous humor (AH) of normal mice were phenotyped in terms of the expression CD4, CD8, CD25, CD127 and transcription factor Foxp3. The mean percentage of CD8+ T cells in the total AH lymphocyte population was as high as 28...
2017: PloS One
https://www.readbyqxmd.com/read/28080210/pathogen-control-at-the-intestinal-mucosa-h2o2-to-the-rescue
#16
Ulla G Knaus, Rosanne Hertzberger, Gratiela G Pircalabioru, S Parsa M Yousefi, Filipe Branco Dos Santos
Intestinal infections are a global challenge, connected to malnutrition and inadequate hygiene in developing countries, and to expanding antibiotic resistance in developed countries. In general, a healthy host is capable of fighting off gut pathogens or at least to recover from infections quickly. The underlying protective mechanism, termed colonization resistance, is provided by indigenous commensal communities (microbiota) that are shaped and aided by the host's epithelial and innate immune system. (1) Commensal-pathogen interactions are governed by competition for a suitable niche for replication and stable colonization, nutrient availability, species-specific alterations of the metabolic environment, changes in oxygen tension and release of chemicals and proteinaceous toxins (bacteriocins)...
January 12, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28079888/antiphospholipid-antibodies-enhance-rat-neonatal-cardiomyocyte-apoptosis-in-an-in-vitro-hypoxia-reoxygenation-injury-model-via-p38-mapk
#17
Lauren T Bourke, Thomas McDonnell, James McCormick, Charis Pericleous, Vera M Ripoll, Ian Giles, Anisur Rahman, Anastasis Stephanou, Yiannis Ioannou
A significant amount of myocardial damage during a myocardial infarction (MI) occurs during the reperfusion stage, termed ischaemia/reperfusion (I/R) injury, and accounts for up to 50% of total infarcted tissue post-MI. During the reperfusion phase, a complex interplay of multiple pathways and mechanisms is activated, which ultimately leads to cell death, primarily through apoptosis. There is some evidence from a lupus mouse model that lupus IgG, specifically the antiphospholipid (aPL) antibody subset, is pathogenic in mesenteric I/R injury...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28079251/maturation-associated-gene-expression-profiles-along-normal-human-bone-marrow-monopoiesis
#18
Fabiana V Mello, Liliane R Alves, Marcelo G P Land, Cristina Teodósio, María-Luz Sanchez, Paloma Bárcena, Rodrigo T Peres, Carlos E Pedreira, Elaine S Costa, Alberto Orfao
Human monopoiesis is a tightly coordinated process which starts in the bone marrow (BM) haematopoietic stem cell (HSC) compartment and leads to the production of circulating blood mature monocytes. Although mature monocytes/macrophages have been extensively studied in both normal or inflammatory conditions, monopoiesis has only been assessed in vitro and in vivo animal models, due to low frequency of the monocytic precursors in the normal human BM. Here we investigated the transcriptional profile along normal human BM monopoiesis...
January 12, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28077577/extracellular-microrna-signature-of-human-helper-t-cell-subsets-in-health-and-autoimmunity
#19
Anna Torri, Donatella Carpi, Elisabetta Bulgheroni, Maria-Cristina Crosti, Monica Moro, Paola Gruarin, Riccardo L Rossi, Grazisa Rossetti, Dolores Di Vizio, Mirjam Hoxha, Valentina Bollati, Cristina Gagliani, Carlo Tacchetti, Moira Paroni, Jens Geginat, Laura Corti, Luigia Venegoni, Emilio Berti, Massimiliano Pagani, Giuseppe Matarese, Sergio Abrignani, Paola de Candia
Upon TCR stimulation, CD4+ T lymphocytes release extracellular vesicles (EVs) containing microRNAs. However, no data are available on whether human CD4+ T cell subsets release EVs containing different pattern of microRNAs. The present work aimed at filling this gap by assessing the microRNA content in EVs released upon in vitro TCR stimulation of Th1, Th17 and T regulatory (Treg) cells. Our results indicate that EVs released by Treg cells are significantly different compared to those released by the other subsets...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28077081/antigen-presenting-capacity-of-murine-splenic-myeloid-cells
#20
Ying-Ying Hey, Benjamin Quah, Helen C O'Neill
BACKGROUND: The spleen is an important site for hematopoiesis. It supports development of myeloid cells from bone marrow-derived precursors entering from blood. Myeloid subsets in spleen are not well characterised although dendritic cell (DC) subsets are clearly defined in terms of phenotype, development and functional role. Recently a novel dendritic-like cell type in spleen named 'L-DC' was distinguished from other known dendritic and myeloid cells by its distinct phenotype and developmental origin...
January 11, 2017: BMC Immunology
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