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https://www.readbyqxmd.com/read/28431214/interferon-%C3%AE-released-by-activated-cd8-t-lymphocytes-impairs-the-calcium-resorption-potential-of-osteoclasts-in-calcified-human-aortic-valves
#1
Edit Nagy, Yang Lei, Eduardo Martínez-Martínez, Simon C Body, Florian Schlotter, Michael Creager, Alexander Assmann, Kamal Khabbaz, Peter Libby, Göran K Hansson, Elena Aikawa
Calcium content in patients with calcific aortic valve disease (CAVD) correlates with the severity of stenosis. In CAVD, activated T lymphocytes localize with osteoclast regions; however, the functional consequences of this association remain unknown. We hypothesized that CD8(+) T cells modulate calcification in CAVD. Explanted CAVD valves (n = 52) dissected into noncalcified and calcified portions were subjected to mRNA extraction, real-time quantitative PCR, enzyme-linked immunosorbent assay, and immunohistochemical analyses...
April 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28431019/identifying-cytomegalovirus-cmv-complications-using-the-quantiferon-cmv-assay-after-allogeneic-hematopoietic-stem-cell-transplantation
#2
Michelle K Yong, Paul U Cameron, Monica Slavin, C Orla Morrissey, Krystal Bergin, Andrew Spencer, David Ritchie, Allen C Cheng, Assia Samri, Guislaine Carcelain, Brigitte Autran, Sharon R Lewin
Background: Cytomegalovirus (CMV) reactivation and disease remain a major cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. A simple test to identify recovery of CMV-specific T-cell immunity could assist clinicians in managing CMV-related complications. Methods: In an observational multi-centre prospective study of 94 allogeneic HSCT recipients we evaluated CMV-specific T-cell immunity at baseline, 3, 6, 9 and 12 months post-transplant using the Quantiferon-CMV®, an ELISpot assay and in a subset, we also evaluated intracellular cytokine staining (ICS)...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28431010/clinical-trial-of-the-anti-pd-l1-antibody-bms-936559-in-hiv-1-infected-participants-on-suppressive-antiretroviral-therapy
#3
Cynthia L Gay, Ronald J Bosch, Justin Ritz, Jason M Hataye, Evgenia Aga, Randall L Tressler, Stephen W Mason, Carey K Hwang, Dennis M Grasela, Neelanjana Ray, Josh C Cyktor, John M Coffin, Edward P Acosta, Richard A Koup, John W Mellors, Joseph J Eron
Background.: Reversing immune exhaustion with an anti-PD-L1 antibody may improve HIV-1-specific immunity and increase clearance of HIV-1 expressing cells. Methods.: Phase I, randomized, double-blind, placebo-controlled dose-escalating study of BMS-936559including HIV-1-infected adults ≥18 to ≤70 years on suppressive antiretroviral therapy with CD4+ counts ≥350 cells/μL and detectable plasma HIV-1 RNA by single copy assay. Data on single infusions of BMS-936559 (0...
April 18, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28430604/signal-transducing-adaptor-protein-2-promotes-generation-of-functional-long-term-memory-cd8-t-cells-by-preventing-terminal-effector-differentiation
#4
Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Chisaki Hyuga-Amaike, Kana Okamori, Isao Tawara, Naozumi Harada, Hiroshi Shiku
Long-surviving memory CD8+ T cells generated by stimulation with appropriate tumor-associated antigens are the most aggressive and persistent tumoricidal effectors. In this event of memory CD8+ T cell development, the signal transducer and activator of transcription (STAT) proteins function as the crucial intracellular signaling molecules, but the regulatory mechanism of STATs in CD8+ T cells is not fully understood. In this study, we report for the first time, by using murine vaccination models, that signal-transducing adaptor protein-2 (STAP2) maintains the cytotoxicity of long-lived memory CD8+ T cells by controlling a STAT3/suppressor of cytokine signaling 3 (SOCS3) cascade...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#5
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28429765/repolarizing-macrophages-improves-breast-cancer-therapy
#6
Luca Cassetta, Jeffrey W Pollard
Tumor-associated macrophages (TAMs) contribute to breast cancer progression and dissemination; TAM-targeting strategies aimed at their reprogramming show promising preclinical results. In a new report Guerriero and colleagues demonstrate that a novel HDAC Class IIa inhibitor, TMP195, can reprogram monocytes and macrophages in the tumor into cells able to sustain a robust CD8 T cell-mediated anti-tumoral immune response.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429464/inflammatory-features-of-frontal-fibrosing-alopecia
#7
Sophia A Ma, Sotonye Imadojemu, Kenneth Beer, John T Seykora
INTRODUCTION: Frontal fibrosing alopecia (FFA) is a cicatricial alopecia typically occurring in post-menopausal women. The etiology and pathophysiology of FFA is poorly understood but thought to be immune mediated. This study aims to further explore the extent of fibrosis and the inflammatory microenvironment by characterizing Langerhans cells (LCs), helper T cells, cytotoxic T cells, and B cells near hair follicles in FFA. METHODS: 11 paraffin-embedded tissues from patients with a clinical and histopathologic diagnosis of FFA were selected for immunohistochemical studies using CD3, CD4, CD8, CD1a, and CD20...
April 21, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#8
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428882/differential-phenotypes-of-memory-cd4-and-cd8-t-cells-in-the-spleen-and-peripheral-tissues-following-immunostimulatory-therapy
#9
Gail D Sckisel, Annie Mirsoian, Christine M Minnar, Marka Crittenden, Brendan Curti, Jane Q Chen, Bruce R Blazar, Alexander D Borowsky, Arta M Monjazeb, William J Murphy
BACKGROUND: Studies assessing immune parameters typically utilize human PBMCs or murine splenocytes to generate data that is interpreted as representative of immune status. Using splenocytes, we have shown memory CD4-T cells that expand following systemic immunostimulatory therapies undergo rapid IFNg-mediated activation induced cell death (AICD) resulting in a net loss of total CD4-T cells which correlates with elevated PD-1 expression. This is in contrast to CD8-T cells which expand with minimal PD-1 upregulation and apoptosis...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428880/long-term-complete-remission-with-ipilimumab-in-metastatic-castrate-resistant-prostate-cancer-case-report-of-two-patients
#10
Luc Cabel, Elika Loir, Gwenaelle Gravis, Pernelle Lavaud, Christophe Massard, Laurence Albiges, Giulia Baciarello, Yohann Loriot, Karim Fizazi
BACKGROUND: Prostate cancer is one of the most common cancers in men and the fourth leading cause of cancer mortality worldwide. Although major progress has been achieved in the last years for patients with metastatic castrate-resistant prostate cancer (mCRPC), thanks to next-generation androgen receptor axis targeted drugs, taxanes, and bone-targeted agents, immunotherapy has not been widely approved and used for the treatment of prostate cancer. Two large studies with ipilimumab, an anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4) antibody reported improved progression-free survival, but not statistically improved overall survival at the primary analysis (CA184 043 and CA184 095)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428786/challenge-of-humans-with-wild-type-salmonella-enterica-serovar-typhi-elicits-changes-in-the-activation-and-homing-characteristics-of-mucosal-associated-invariant-t-cells
#11
Rosângela Salerno-Goncalves, David Luo, Stephanie Fresnay, Laurence Magder, Thomas C Darton, Claire Jones, Claire S Waddington, Christoph J Blohmke, Brian Angus, Myron M Levine, Andrew J Pollard, Marcelo B Sztein
Gastrointestinal infections by Salmonella enterica serovar Typhi (S. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.9 million new cases annually and significant mortality when untreated. Recently, we provided the first direct evidence that CD8(+) MAIT cells are activated and have the potential to kill cells exposed to S. Typhi, and that these responses are dependent on bacterial load. However, MAIT cell kinetics and function during bacterial infections in humans remain largely unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28428619/transcriptomic-analysis-reveals-a-previously-unknown-role-for-cd8-t-cells-in-rvsv-ebov-mediated-protection
#12
Andrea R Menicucci, Suhas Sureshchandra, Andrea Marzi, Heinz Feldmann, Ilhem Messaoudi
Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced with EBOV GP (rVSV-EBOV) is safe and highly efficacious. We previously established that antibodies are essential for rVSV-EBOV mediated protection against EBOV; however, the mechanisms by which this vaccine induces a humoral response and the role of T-cells in rVSV-EBOV mediated protection remain poorly understood...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428537/human-cytomegalovirus-induces-cellular-and-humoral-virus-specific-immune-responses-in-humanized-blt-mice
#13
Lindsey B Crawford, Rebecca Tempel, Daniel N Streblow, Craig Kreklywich, Patricia Smith, Louis J Picker, Jay A Nelson, Patrizia Caposio
The strict species specificity of Human Cytomegalovirus (HCMV) has impeded our understanding of antiviral adaptive immune responses in the context of a human immune system. We have previously shown that HCMV infection of human hematopoietic progenitor cells engrafted in immune deficient mice (huNSG) results in viral latency that can be reactivated following G-CSF treatment. In this study, we characterized the functional human adaptive immune responses in HCMV latently-infected huBLT (humanized Bone marrow-Liver-Thymus) mice...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428275/epithelial-to-mesenchymal-transition-contributes-to-immunosuppression-in-breast-carcinomas
#14
Anushka Dongre, Mohammad Rashidian, Ferenc Reinhardt, Aaron Bagnato, Zuzana Keckesova, Hidde L Ploegh, Robert A Weinberg
The Epithelial-to-mesenchymal transition (EMT) is a cell-biological program that confers mesenchymal traits on carcinoma cells and drives their metastatic dissemination. It is, unclear, however, whether activation of EMT in carcinoma cells can change their susceptibility to immune attack. We demonstrate here that mammary tumor cells arising from more epithelial carcinoma cell lines expressed high levels of MHC-I, low levels of PD-L1 and contained within their stroma CD8+ T cells and M1 (anti-tumor) macrophages...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#15
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28428135/the-immunotoxicological-pattern-of-subchronic-and-chronic-benzene-exposure-in-rats
#16
Alexander V Karaulov, Irina V Mikhaylova, Alexander I Smolyagin, Viktor M Boev, Alexandra Kalogeraki, Aristides M Tsatsakis, Ayse Basak Engin
Exposure to benzene and its inevitable metabolites can result in deleterious effects on human health, including lymphocytopenia, hematotoxicity and cancer. However, the duration of exposure might alter the effects including immune consequences. The aim of this study was to determine whether benzene could modulate lymphocyte proliferation induced by the T cell mitogen concanavalin A, in rats, at different exposure durations. 386 Wistar rats were assigned into control and treatment groups which was subdivided into groups for 45, 90 and 135days for 0,6mL/kg of drinking water mixed benzene treatment...
April 17, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28428120/pathogenesis-of-immune-thrombocytopenia
#17
REVIEW
Sylvain Audia, Matthieu Mahévas, Maxime Samson, Bertrand Godeau, Bernard Bonnotte
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigen-presenting cell during ITP. CD8(+) T cells also participate to thrombocytopenia by increasing platelet apoptosis...
April 17, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28428066/effects-of-gold-nanoparticle-based-vaccine-size-on-lymph-node-delivery-and-cytotoxic-t-lymphocyte-responses
#18
Sukmo Kang, Sukyung Ahn, Jeewon Lee, Jinyong Kim, Minsuk Choi, Vipul Gujrati, Hyungjun Kim, Jinjoo Kim, Eui-Cheol Shin, Sangyong Jon
Although it has been shown that the size of nanoparticle-based vaccines is a key determining factor for the induction of immune responses, few studies have provided detailed analyses of thresholds or critical sizes of nanoparticle vaccines. Here we report effects of the size of gold nanoparticle (GNP)-based vaccines on their efficiency of delivery to lymph nodes (LNs) and induction of CD8(+) T-cell responses. We further propose a threshold size of GNPs for use as an effective vaccine. To examine the effects of GNP size, we synthesized GNPs with diameters of 7, 14 and 28nm, and then conjugated them with recombinant ovalbumin (OVA) as a model antigen...
April 17, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28427861/divergent-function-of-programmed-death-ligand-1-in-donor-tissue-versus-recipient-immune-system-in-a-murine-model-of-bronchiolitis-obliterans
#19
Katharina Schütte-Nütgen, Olaf Boenisch, Hakima Harrach, Alicia Casey, Indira Guleria, Nader Najafian, Mohamed H Sayegh, Craig J Gerard, Meera Subramaniam
Costimulatory molecules, such as the programmed death ligand (PD-L1), might exert differential effects on T-cell function, depending on the clinical setting and/or immunological environment. Given the impact of T cells on bronchiolitis obliterans (BO) in lung transplantation, we used an established tracheal transplant model inducing BO-like lesions to investigate the impact of PD-L1 on alloimmune responses and histopathological outcome in BO. In contrast to other transplant models in which PD-L1 generally shows protective functions, we demonstrated that PD-L1 has divergent effects depending on its location in donor versus recipient tissue...
April 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28427753/prognostic-markers-in-oropharyngeal-squamous-cell-carcinoma-focus-on-cd70-and-tumour-infiltrating-lymphocytes
#20
Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Karen Zwaenepoel, Philippe Deron, Fréderic Duprez, Sylvie Rottey, Liesbeth Ferdinande
We evaluated the expression of CD70 as biomarker for prognosis in patients with oropharyngeal squamous cell carcinoma (OSCC). We also examined the prognostic value of tumour infiltrating lymphocytes (TILs) in our study cohort. Formalin fixed, paraffin embedded tissue originating from the oropharynx of 78 patients was immunohistochemically stained for CD70, CD3, CD8 and FoxP3. Expression of CD70, CD3, CD8, FoxP3 and HPV status was correlated with clinicopathological characteristics. Overall survival (OS) was determined by a log-rank (Mantel-Cox) test whereas the Cox proportional hazard model was used for multivariate analysis...
April 17, 2017: Pathology
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