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T cell exhaustion

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https://www.readbyqxmd.com/read/29341423/variable-immune-deficiency-related-to-deletion-size-in-chromosome-22q11-2-deletion-syndrome
#1
Blaine Crowley, Melanie Ruffner, Donna M McDonald McGinn, Kathleen E Sullivan
The clinical features of 22q11.2 deletion syndrome include virtually every organ of the body. This review will focus on the immune system and the differences related to deletion breakpoints. A hypoplastic thymus was one of the first features described in this syndrome and low T cell counts, as a consequence of thymic hypoplasia, are the most commonly described immunologic feature. These are most prominently seen in early childhood and can be associated with increased persistence of viruses. Later in life, evidence of T cell exhaustion may be seen and secondary deficiencies of antibody function have been described...
January 17, 2018: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29340006/the-impact-of-the-progressive-efficiency-test-on-a-rowing-ergometer-on-white-blood-cells-distribution-and-clinical-chemistry-changes-in-paralympic-rowers-during-the-preparatory-stage-before-the-paralympic-games-in-rio-2016-a-case-report
#2
Robert Nowak, Rafał Buryta, Krzysztof Krupecki, Tomasz Zając, Marek Zawartka, Patrizia Proia, Dorota Kostrzewa-Nowak
There is a large gap in knowledge regarding research on post-exercise blood changes in disabled athletes. There are relatively few data on adaptive mechanisms to exercise in disabled athletes, including disabled rowers. Two rowers from a Polish adaptive rowing settle TAMix2x that qualified for the Paralympic Games in Rio, 2016 took part in this study. They performed a progressive test on a rowing ergometer until exhaustion. The cardiorespiratory fitness measures, complete blood count, white blood cells' distribution and 30 clinical chemistry variables describing laboratory diagnostic profiles and general health were determined...
December 2017: Journal of Human Kinetics
https://www.readbyqxmd.com/read/29339767/regulatory-t-cells-trigger-effector-t-cell-dna-damage-and-senescence-caused-by-metabolic-competition
#3
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C Hsueh, Daniel F Hoft, Guangyong Peng
Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29338031/pre-existing-malignancy-results-in-increased-prevalence-of-distinct-populations-of-cd4-t-cells-during-sepsis
#4
Jianfeng Xie, Jennifer M Robertson, Ching-Wen Chen, Wenxiao Zhang, Craig M Coopersmith, Mandy L Ford
The presence of pre-existing malignancy in murine hosts results in increased immune dysregulation and risk of mortality following a septic insult. Based on the known systemic immunologic changes that occur in cancer hosts, we hypothesized that the presence of pre-existing malignancy would result in phenotypic and functional changes in CD4+ T cell responses following sepsis. In order to conduct a non-biased, unsupervised analysis of phenotypic differences between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor cells and tumors were allowed to grow for 3 weeks...
2018: PloS One
https://www.readbyqxmd.com/read/29335088/-role-of-programmed-death-1-in-viral-infectious-diseases
#5
Fu-Ce Lu, Guang-Min Nong
The research on the immunoregulatory effect of programmed death-1 (PD-1) in infectious diseases mainly focuses on chronic viral infection, but there are few studies on acute viral infection. In chronic viral infection, PD-1 is highly expressed on the surface of CD8+ T cells, which is a sign of CD8+ T cell depletion. Recent studies have shown that in chronic viral infection, PD-1 is also highly expressed on the surface of regulatory T cells and binds to programmed death-ligand 1 (PD-L1) on the surface of exhausted CD8+ T cells, resulting in a stronger inhibitory effect on CD8+ T cell immunity...
January 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29330114/human-cd4-cd25-cd127hi-cells-and-the-th1-th2-phenotype
#6
Aditi Narsale, Rosita Moya, Joanna Davida Davies
CD4+ T cells that co-express CD25 and CD127 (CD25+CD127+) make up around 20% of all circulating CD4+ memory T cells in healthy people. The clinical significance of these cells is that in children with type 1 diabetes their relative frequency at diagnosis is significantly and directly correlated with rate of disease progression. The purpose of this study was to further characterize the CD25+CD127hi cells. We show that they are a mix of Th1 and Th2 cells however, they have a significantly higher relative frequency of pre-committed and committed Th2 cells, and secrete significantly higher levels of Th2-type cytokines than CD25- memory T cells...
January 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29329113/therapeutic-hiv-1-vaccine-time-for-immunomodulation-and-combinatorial-strategies
#7
Nabila Seddiki, Yves Lévy
PURPOSE OF REVIEW: The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells...
January 10, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29328499/mait-cells-are-chronically-activated-in-patients-with-autoimmune-liver-disease-and-promote-pro-fibrogenic-hepatic-stellate-cell-activation
#8
Katrin Böttcher, Krista Rombouts, Francesca Saffioti, Davide Roccarina, Matteo Rosselli, Andrew Hall, TuVinh Luong, Emmanuel A Tsochatzis, Douglas Thorburn, Massimo Pinzani
Autoimmune liver diseases (AILD) are chronic liver pathologies characterised by fibrosis and cirrhosis due to immune-mediated liver damage. In this study, we addressed the question whether mucosal-associated invariant T (MAIT) cells, innate-like T cells, are functionally altered in patients with AILD and whether MAIT cells can promote liver fibrosis through activation of hepatic stellate cells. We analysed the phenotype and function of MAIT cells from AILD patients and healthy controls by multi-colour flow cytometry and investigated the interaction between human MAIT cells and primary human hepatic stellate cells (hHSCs)...
January 12, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29324842/effect-of-analytical-treatment-interruption-and-reinitiation-of-antiretroviral-therapy-on-hiv-reservoirs-and-immunologic-parameters-in-infected-individuals
#9
Katherine E Clarridge, Jana Blazkova, Kevin Einkauf, Mary Petrone, Eric W Refsland, J Shawn Justement, Victoria Shi, Erin D Huiting, Catherine A Seamon, Guinevere Q Lee, Xu G Yu, Susan Moir, Michael C Sneller, Mathias Lichterfeld, Tae-Wook Chun
Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV remission in infected individuals are under active investigation. Considering the vast majority of HIV-infected individuals experience plasma viral rebound upon cessation of therapy, clinical trials evaluating the efficacy of curative strategies would likely require inclusion of ART interruption. However, it is unclear what impact short-term analytical treatment interruption (ATI) and subsequent reinitiation of ART have on immunologic and virologic parameters of HIV-infected individuals...
January 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29323266/aif-loss-deregulates-hematopoiesis-and-reveals-different-adaptive-metabolic-responses-in-bone-marrow-cells-and-thymocytes
#10
Lauriane Cabon, Audrey Bertaux, Marie-Noëlle Brunelle-Navas, Ivan Nemazanyy, Laurianne Scourzic, Laure Delavallée, Laura Vela, Mathieu Baritaud, Sandrine Bouchet, Cécile Lopez, Vu Quang Van, Kevin Garbin, Danielle Chateau, Françoise Gilard, Marika Sarfati, Thomas Mercher, Olivier A Bernard, Santos A Susin
Mitochondrial metabolism is a tightly regulated process that plays a central role throughout the lifespan of hematopoietic cells. Herein, we analyze the consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism disorder associated with the cell-specific hematopoietic ablation of apoptosis-inducing factor (AIF). AIF-null (AIF-/Y ) mice developed pancytopenia that was associated with hypocellular bone marrow (BM) and thymus atrophy. Although myeloid cells were relatively spared, the B-cell and erythroid lineages were altered with increased frequencies of precursor B cells, pro-erythroblasts I, and basophilic erythroblasts II...
January 11, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#11
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311234/mycoplasma-bovis-induced-inhibition-of-bovine-pbmc-proliferation-is-ameliorated-after-blocking-the-immune-inhibitory-programmed-death-1-pd-1-receptor
#12
Muhammad Suleman, Farhan S Cyprian, Steve Jimbo, Teresia Maina, Tracy Prysliak, Claire Windeyer, Jose Perez-Casal
Mycoplasma bovis (M. bovis) induced-immune suppression is a major obstacle faced by the host for controlling infections. M. bovis impairment of antigen-specific T-cells responses is achieved through inhibiting the proliferation of peripheral-blood mononuclear cells (PBMC). This impairment may contribute to the persistence of M. bovis infection in various sites including lungs and its systemic spread to various organs like joints, with the underlying mechanisms remaining elusive. Here, we elucidated the role of the immune-inhibitory receptor programmed death-1 (PD-1) and its ligand (PD-L1) in M...
January 8, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29309050/hepatitis-b-virus-specific-t-cells-associate-with-viral-control-upon-nucleos-t-ide-analogue-therapy-discontinuation
#13
Laura Rivino, Nina Le Bert, Upkar S Gill, Kamini Kunasegaran, Yang Cheng, Damien Zm Tan, Etienne Becht, Navjyot K Hansi, Graham R Foster, Tung-Hung Su, Tai-Chung Tseng, Seng Gee Lim, Jia-Horng Kao, Evan W Newell, Patrick Tf Kennedy, Antonio Bertoletti
BACKGROUND: The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which patients nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, therapy discontinuation can be associated with virological and biochemical relapse and, consequently, therapy in the majority is life-long. METHODS: Since antiviral immunity is pivotal for HBV control, we investigated potential biomarkers for the safe discontinuation of NUCs within immune profiles of chronic HBV patients by utilizing traditional immunological assays (ELISPOT, flow cytometry) in conjunction with analyses of global non-antigen-specific immune populations (NanoString and CyTOF)...
January 8, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29308317/high-numbers-of-pdcd1-pd-1-positive-t-cells-and-b2m-mutations-in-microsatellite-unstable-colorectal-cancer
#14
Jonas Janikovits, Meike Müller, Julia Krzykalla, Sandrina Körner, Fabian Echterdiek, Bernd Lahrmann, Niels Grabe, Martin Schneider, Axel Benner, Magnus von Knebel Doeberitz, Matthias Kloor
DNA mismatch repair (MMR)-deficient cancers accumulate high numbers of coding microsatellite mutations, which lead to the generation of highly immunogenic frameshift peptide (FSP) neoantigens. MMR-deficient cells can grow out to clinically manifest cancers either if they evade immune cell attack or if local T-cells get exhausted. Therefore, a subset of MSI cancer patients responds particularly well to treatment with immune checkpoint inhibitors. We analyzed whether immune evasion in MMR-deficient cancer mediated by loss of HLA class I or II antigens is related to local immune cell activation status...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29308300/co-stimulatory-signaling-determines-tumor-antigen-sensitivity-and-persistence-of-car-t-cells-targeting-psca-metastatic-prostate-cancer
#15
Saul J Priceman, Ethan A Gerdts, Dileshni Tilakawardane, Kelly T Kennewick, John P Murad, Anthony K Park, Brook Jeang, Yukiko Yamaguchi, Xin Yang, Ryan Urak, Lihong Weng, Wen-Chung Chang, Sarah Wright, Sumanta Pal, Robert E Reiter, Anna M Wu, Christine E Brown, Stephen J Forman
Advancing chimeric antigen receptor (CAR)-engineered adoptive T cells for the treatment of solid cancers is a major focus in the field of immunotherapy, given impressive recent clinical responses in hematological malignancies. Prostate cancer may be amenable to T cell-based immunotherapy since several tumor antigens, including prostate stem-cell antigen (PSCA), are widely over-expressed in metastatic disease. While antigen selectivity of CARs for solid cancers is crucial, it is problematic due to the absence of truly restricted tumor antigen expression and potential safety concerns with "on-target off-tumor" activity...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29296862/brafv600e-accelerates-disease-progression-and-enhances-immune-suppression-in-a-mouse-model-of-b-cell-leukemia
#16
Yo-Ting Tsai, Aparna Lakshmanan, Amy Lehman, Bonnie K Harrington, Fabienne McClanahan Lucas, Minh Tran, Ellen J Sass, Meixiao Long, Alan D Flechtner, Florinda Jaynes, Krista La Perle, Vincenzo Coppola, Gerard Lozanski, Natarajan Muthusamy, John C Byrd, Michael R Grever, David M Lucas
Mutated mitogen-activated protein kinase (MAPK) pathway components promote tumor survival, proliferation, and immune evasion in solid tumors. MAPK mutations occur in hematologic cancers as well, but their role is less clear and few models are available to study this. We developed an in vivo model of disseminated BRAFV600E B-cell leukemia to determine the effects of this mutation on tumor development and immune evasion. Mice with B-cell-restricted BRAFV600E expression crossed with the Eµ-TCL1 model of chronic lymphocytic leukemia (CLL) developed leukemia significantly earlier (median, 4...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29282694/immune-checkpoint-blockade-in-breast-cancer-therapy
#17
Xia Bu, Yihui Yao, Xiaoyu Li
Cancer immunotherapy is emerging as the most promising novel strategy for cancer treatment. Cancer immunotherapy is broadly categorized into three forms: immune checkpoint modulation, adoptive cell transfer, and cancer vaccine. Immune checkpoint blockade is demonstrated as the most clinically effective treatment with low immune-related adverse events (irAE). Blockade of PD-1/PD-L1 and CTLA-4 has achieved remarkable success in treating various types of tumors, which sparks great interests in this therapeutic strategy and expands the role of immune checkpoint blockade in treating tumors including breast cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29276179/cd4-t-cells-are-exhausted-and-show-functional-defects-in-chronic-lymphocytic-leukemia
#18
Esmaeil Allahmoradi, Saeid Taghiloo, Mohsen Tehrani, Hadi Hossein-Nattaj, Ghasem Janbabaei, Ramin Shekarriz, Hossein Asgarian-Omran
BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western world. This health problem is caused due to the accumulation of mature B-lymphocytes in the peripheral blood and bone marrow. In the course of cancer, CD4+ T cells become "exhausted" and characterized with poor effector functions and the expression of multiple inhibitory receptors. OBJECTIVE: To investigate the frequency and functional properties of exhausted CD4+ T lymphocytes in patients with CLL...
December 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/29274296/t-cell-exhaustion-in-cancer-mechanisms-and-clinical-implications
#19
Jin-Cheng Wang, Yong Xu, Zheng-Ming Huang, Xiao-Jie Lu
During chronic viral infection or cancer, the immune system usually induces a corresponding immune response against pathogens or cancer cells so as to prevent worsening disease. T cell exhaustion in which reduced and dysfunctional effector T cells lead to immune escape is one of the mechanisms that pathogens or cancer cells get rid of control from the immune system. In this review, we discuss some mechanisms associated with T cell exhaustion and enumerate current methods of reversing T cell exhaustion. We also summarize current targeted treatment strategies and put forward following aspects that required to research...
December 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29273341/current-concepts-on-immunopathogenesis-of-hepatitis-b-virus-infection
#20
REVIEW
Hadi Peeridogaheh, Zahra Meshkat, Shahram Habibzadeh, Mohsen Arzanlou, Jafar Mohammad Shahi, Sina Rostami, Sina Gerayli, Roghayeh Teimourpour
Hepatitis B virus (HBV) infection is a leading cause of liver damage and hepatic inflammation. Upon infection, effective antiviral responses by CD8+ T cells, CD4+ T cells, Natural killer (NK) cells, and monocytes can lead to partial or complete eradication of the viral infection. To date, many studies have shown that the production of inhibitory cytokines such as Interleukin 10 (IL-10), Transforming growth factor beta (TGF-β), along with dysfunction of the dendritic cells (DCs), and the absence of efficient innate immune responses could lead to T cell exhaustion, development of persistent infection, and inability to eradicate the viral infection from liver...
December 19, 2017: Virus Research
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