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Exhausted T cell

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https://www.readbyqxmd.com/read/28822763/activating-transcription-factor-3-regulates-chemokine-expression-in-contracting-c2c12-myotubes-and-in-mouse-skeletal-muscle-after-eccentric-exercise
#1
R Fernández-Verdejo, A M Vanwynsberghe, T Hai, L Deldicque, M Francaux
Activating transcription factor (ATF) 3 regulates chemokine expression in various cell types and tissues. Herein, we studied this regulation in contracting muscle cells in vitro, and in skeletal muscle after muscle-damaging exercise in vivo. C2C12 myotubes with normal or low ATF3 levels (atf3_siRNA) were electrically stimulated (EPS). Also, ATF3-knockout (ATF3-KO) and control mice ran downhill until exhaustion, and muscles were analyzed post-exercise. EPS increased ATF3 levels in myotubes (P < 0.01)...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28821806/longitudinal-study-of-changes-in-%C3%AE-%C3%AE-t-cells-and-cd4-t-cells-upon-asymptomatic-malaria-infection-in-indonesian-children
#2
Sanne E de Jong, Vera E R Asscher, Linda J Wammes, Aprilianto E Wiria, Firdaus Hamid, Erliyani Sartono, Taniawati Supali, Hermelijn H Smits, Adrian J F Luty, Maria Yazdanbakhsh
Both γδ T cells and CD4(+) T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of γδ T cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. Infected children also had higher levels of Th1 and Th17 cells, lower levels of CD25(Hi) FOXP3(+) regulatory T cells (Tregs), but similar levels of Th2 cells as compared to uninfected children...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821503/anti-ctla4-and-anti-pd-1-act-on-distinct-t-cell-populations
#3
(no author information available yet)
Both anti-PD-1 and anti-CTLA4 target subpopulations of exhausted-like CD8(+) T cells.
August 18, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28806406/terminal-differentiation-of-t-cells-is-strongly-associated-with-cmv-infection-and-increased-in-hiv-positive-individuals-on-art-and-lifestyle-matched-controls
#4
Thijs Booiman, Ferdinand W Wit, Arginell F Girigorie, Irma Maurer, Davide De Francesco, Caroline A Sabin, Agnes M Harskamp, Maria Prins, Claudio Franceschi, Steven G Deeks, Alan Winston, Peter Reiss, Neeltje A Kootstra
HIV-1-positive individuals on successful antiretroviral therapy (ART) are reported to have higher rates of age-associated non-communicable comorbidities (AANCCs). HIV-associated immune dysfunction has been suggested to contribute to increased AANCC risk. Here we performed a cross-sectional immune phenotype analysis of T cells in ART-treated HIV-1-positive individuals with undetectable vireamia (HIV-positives) and HIV-1-negative individuals (HIV-negatives) over 45 years of age. In addition, two control groups were studied: HIV negative adults selected based on lifestyle and demographic factors (Co-morBidity in Relation to AIDS, or COBRA) and unselected age-matched donors from a blood bank...
2017: PloS One
https://www.readbyqxmd.com/read/28803728/distinct-cellular-mechanisms-underlie-anti-ctla-4-and-anti-pd-1-checkpoint-blockade
#5
Spencer C Wei, Jacob H Levine, Alexandria P Cogdill, Yang Zhao, Nana-Ama A S Anang, Miles C Andrews, Padmanee Sharma, Jing Wang, Jennifer A Wargo, Dana Pe'er, James P Allison
Immune-checkpoint blockade is able to achieve durable responses in a subset of patients; however, we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4- and anti-PD-1-induced tumor rejection. To address these issues, we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor-infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor-infiltrating T cell populations...
August 9, 2017: Cell
https://www.readbyqxmd.com/read/28800954/a-tim-3-oligonucleotide-aptamer-enhances-t-cell-functions-and-potentiates-tumor-immunity-in-mice
#6
Tal Gefen, Iris Castro, Darija Muharemagic, Yvonne Puplampu-Dove, Shradha Patel, Eli Gilboa
T cell immunoglobulin-3 (TIM-3) is a negative regulator of interferon-γ (IFN-γ) secreting CD4(+) T cells and CD8(+) T cytotoxic cells. Recent studies have highlighted the role of TIM-3 as an important mediator of CD8(+) T cell exhaustion in the setting of chronic viral infections and cancer. In murine tumor models, antibody blockade of TIM-3 with anti-TIM-3 antibodies as monotherapy has no or minimal antitumor activity, suggesting that TIM-3 signaling exerts an accessory or amplifying effect in keeping immune responses in check...
August 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28797787/t-cell-exhaustion-an-epigenetically-imprinted-phenotypic-and-functional-makeover
#7
Francesca Alfei, Dietmar Zehn
A recent article in Cell demonstrates that the absence of a single DNA methyltransferase, Dnmt3a, prevents cytotoxic T cells from acquiring the hypofunctional or exhausted phenotype typically seen in chronic viral infections and tumors. Upon establishing a causal relationship between exhaustion-associated epigenetic changes and reduced CD8(+) T cell function, the authors provided mechanistic evidence that exhaustion constitutes a specific differentiation program.
August 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28794233/characterization-of-mycobacterium-tuberculosis-specific-cells-using-mhc-class-ii-tetramers-reveals-phenotypic-differences-related-to-hiv-infection-and-tuberculosis-disease
#8
Natalie Strickland, Tracey L Müller, Natacha Berkowitz, Rene Goliath, Mary N Carrington, Robert J Wilkinson, Wendy A Burgers, Catherine Riou
A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4(+) T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4(+) T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28791012/extracellular-vesicles-transfer-the-receptor-programmed-death-1-in-rheumatoid-arthritis
#9
Stinne R Greisen, Yan Yan, Aida S Hansen, Morten T Venø, Jens R Nyengaard, Søren K Moestrup, Malene Hvid, Gordon J Freeman, Jørgen Kjems, Bent Deleuran
INTRODUCTION: Extracellular vesicles (EVs) have been recognized as route of communication in the microenvironment. They transfer proteins and microRNAs (miRNAs) between cells, and possess immunoregulatory properties. However, their role in immune-mediated diseases remains to be elucidated. We hypothesized a role for EVs in the rheumatoid arthritis (RA) joint, potentially involving the development of T cell exhaustion and transfer of the co-inhibitory receptor programmed death 1 (PD-1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28780815/-evaluation-of-the-viability-of-beas-2b-cells-exposed-to-gasoline-engine-exhaust-with-different-particle-sizes-by-air-liquid-interface
#10
T Yu, X Y Zhang, Z X Wang, B Li, Y X Zheng, P Bin
Objective: To evaluate the viability of gasoline engine exhaust (GEE) with different particle sizes on human lung cell line BEAS-2B in vitro by air-liquid interface (ALI) . Methods: GEE were collected with a Tedlar bag and their particulate matter (PM) number, surface and mass concentration in three kind of GEE (filtered automobile exhaust, non-filtered automobile exhaust and motorcycle exhaust without three-way catalytic converter) were measured by two type of particle size spectrometer including TSI-3321 and SMPS-3938...
June 20, 2017: Chinese Journal of Industrial Hygiene and Occupational Diseases
https://www.readbyqxmd.com/read/28770269/the-pd-1-pd-l1-inhibitory-pathway-is-altered-in-primary-glomerulonephritides
#11
Ewelina Grywalska, Iwona Smarz-Widelska, Ewelina Krasowska-Zajac, Izabela Korona-Glowniak, Karolina Zaluska-Patel, Michal Mielnik, Martyna Podgajna, Anna Malm, Jacek Rolinski, Wojciech Zaluska
The pathogenesis of primary proliferative and non-proliferative glomerulonephritides (PGN and NPGN) is still not fully understood, however, current evidence suggests that most cases of PGN and NPGN are the results of immunologic response to different etiologic agents that activates various biological processes leading to glomerular inflammation and injury. Programmed cell death protein 1 (PD-1) is the major inhibitory receptor regulating T cell exhaustion. The aim of this study was to evaluate the frequencies of PD-1-positive and PD-ligand 1 (PD-L1)-positive T and B lymphocytes in patients with NPGN and PGN in relation to clinical parameters for the first time...
August 2, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28768188/blockage-of-core-fucosylation-reduces-cell-surface-expression-of-pd-1-and-promotes-anti-tumor-immune-responses-of-t-cells
#12
Masahiro Okada, Shunsuke Chikuma, Taisuke Kondo, Sana Hibino, Hiroaki Machiyama, Tadashi Yokosuka, Miyako Nakano, Akihiko Yoshimura
Programmed cell death 1 (PD-1) is highly expressed on exhausted T cells and inhibits T cell activation. Antibodies that block the interaction between PD-1 and its ligand prevent this inhibitory signal and reverse T cell dysfunction, providing beneficial anti-tumor responses in a substantial number of patients. Mechanisms for the induction and maintenance of high PD-1 expression on exhausted T cells have not been fully understood. Utilizing a genome-wide loss-of-function screening method based on the CRISPR-Cas9 system, we identified genes involved in the core fucosylation pathway as positive regulators of cell-surface PD-1 expression...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28767147/programmed-death-1-is-highly-expressed-on-cd8-cd57-t-cells-in-patients-with-stable-multiple-sclerosis-and-inhibits-their-cytotoxic-response-to-ebv
#13
Maria T Cencioni, Roberta Magliozzi, Richard Nicholas, Rehiana Ali, Omar Malik, Richard Reynolds, Giovanna Borsellino, Luca Battistini, Paolo Muraro
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the CNS of patients with Multiple Sclerosis (pwMS) as a possible cause of disease. In this study, we have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 pwMS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death-1 (PD-1) and human inhibitor receptor Ig-like transcript 2 (ILT2)...
August 2, 2017: Immunology
https://www.readbyqxmd.com/read/28761354/pd-1-blockade-restores-impaired-function-of-ex-vivo-expanded-cd8-t-cells-and-enhances-apoptosis-in-mismatch-repair-deficient-epcam-pd-l1-cancer-cells
#14
Rajeev Kumar, Fang Yu, Yuan-Huan Zhen, Bo Li, Jun Wang, Yuan Yang, Hui-Xin Ge, Ping-Sheng Hu, Jin Xiu
BACKGROUND: Adoptive T cell therapy has been proven to be a promising modality for the treatment of cancer patients in recent years. However, the increased expression of inhibitory receptors could negatively regulate the function and persistence of transferred T cells which mediates T cell anergy, exhaustion, and tumor regression. In this study, we investigated increased cytotoxic activity after the blockade of PD-1 for effective immunotherapy. METHODS: The cytotoxic function of expanded CD8(+) CTLs and interactions with tumor cells investigated after blocking of PD-1...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28758198/mir-15a-16-deficiency-enhances-anti-tumor-immunity-of-glioma-infiltrating-cd8-t-cells-through-targeting-mtor
#15
Jiao Yang, Ronghua Liu, Yuting Deng, Jiawen Qian, Zhou Lu, Yuedi Wang, Dan Zhang, Feifei Luo, Chu Yiwei
MiR-15a/16, a miRNA cluster located at chromosome 13q14, has been reported to act as an immune regulator in inflammatory disorders besides its aberrant expression in cancers. However, little is known about its regulation in tumor-infiltrating immune cells. In this study, using an orthotropic GL261 mouse glioma model, we found that miR-15a/16 deficiency in host inhibited tumor growth and prolonged mice survival, which might be associated with the accumulation of tumor-infiltrating CD8+ T cells. More importantly, tumor-infiltrating CD8+ T cells without miR-15a/16 showed lower expression of PD-1, Tim-3 and LAG-3, and stronger secretion of IFN-γ, IL-2 and TNF-α than WT tumor-infiltrating CD8+ T cells...
July 31, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28750066/cross-modulation-of-pathogen-specific-pathways-enhances-malnutrition-during-enteric-co-infection-with-giardia-lamblia-and-enteroaggregative-escherichia-coli
#16
Luther A Bartelt, David T Bolick, Jordi Mayneris-Perxachs, Glynis L Kolling, Gregory L Medlock, Edna I Zaenker, Jeffery Donowitz, Rose Viguna Thomas-Beckett, Allison Rogala, Ian M Carroll, Steven M Singer, Jason Papin, Jonathan R Swann, Richard L Guerrant
Diverse enteropathogen exposures associate with childhood malnutrition. To elucidate mechanistic pathways whereby enteric microbes interact during malnutrition, we used protein deficiency in mice to develop a new model of co-enteropathogen enteropathy. Focusing on common enteropathogens in malnourished children, Giardia lamblia and enteroaggregative Escherichia coli (EAEC), we provide new insights into intersecting pathogen-specific mechanisms that enhance malnutrition. We show for the first time that during protein malnutrition, the intestinal microbiota permits persistent Giardia colonization and simultaneously contributes to growth impairment...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28747914/extrinsic-protein-tyrosine-phosphatase-non-receptor-22-signals-contribute-to-cd8-t-cell-exhaustion-and-promote-persistence-of-chronic-lymphocytic-choriomeningitis-virus-infection
#17
Tatiana Jofra, Giuseppe Galvani, Mirela Kuka, Roberta Di Fonte, Bechara G Mfarrej, Matteo Iannacone, Shahram Salek-Ardakani, Manuela Battaglia, Georgia Fousteri
A genetic variant of the protein tyrosine phosphatase non-receptor 22 (PTPN22) is associated with a wide range of autoimmune diseases; however, the reasons behind its prevalence in the general population remain not completely understood. Recent evidence highlights an important role of autoimmune susceptibility genetic variants in conferring resistance against certain pathogens. In this study, we examined the role of PTPN22 in persistent infection in mice lacking PTPN22 infected with lymphocytic choriomeningitis virus clone 13...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28736431/combined-blockade-of-t-cell-immunoglobulin-and-mucin-domain-3-and-carcinoembryonic-antigen-related-cell-adhesion-molecule-1-results-in-durable-therapeutic-efficacy-in-mice-with-intracranial-gliomas
#18
Jinhu Li, Xiaodong Liu, Yijun Duan, Yueting Liu, Hongqin Wang, Shizhong Lian, Guotao Zhuang, Yimin Fan
BACKGROUND Glioblastoma multiforme (GBM) evades immune surveillance by inducing immunosuppression via receptor-ligand interactions between immune checkpoint molecules. T cell immunoglobulin and mucin domain 3 (Tim-3) is a key checkpoint receptor responsible for exhaustion and dysfunction of T cells and plays a critical role in immunosuppression. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been recently identified as a heterophilic ligand for Tim-3. MATERIAL AND METHODS We established an intracranial GBM model using C57BL/6 mice and GL261 cells, and treated the mice with single or combined monoclonal antibodies (mAbs) against Tim-3/CEACAM1...
July 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28735813/atypical-memory-b-cells-in-human-chronic-infectious-diseases-an-interim-report
#19
Silvia Portugal, Nyamekye Obeng-Adjei, Susan Moir, Peter D Crompton, Susan K Pierce
Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments...
July 11, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28734175/cd8-t-cell-programming-by-cytomegalovirus-vectors-applications-in-prophylactic-and-therapeutic-vaccination
#20
REVIEW
Klaus Früh, Louis Picker
Vectors based on cytomegalovirus (CMV) represent a novel vaccine platform that maintains high frequencies of non-exhausted effector memory T cells in both CMV sero-positive and sero-negative individuals. In non-human primate models, CMV vectored vaccines provide unprecedented protection against simian immunodeficiency virus (SIV). Moreover, CMV vectors can be genetically altered to program highly diverse CD8+ T cell responses that differ in their epitope targeting including conventional, MHC-I restricted CD8+ T cells as well as unconventional CD8+ T cells restricted by MHC class II or non-polymorphic MHC-E...
July 19, 2017: Current Opinion in Immunology
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