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Exhausted T cell

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https://www.readbyqxmd.com/read/29055013/a-synthetic-cd8%C3%AE-myd88-co-receptor-enhances-cd8-t-cell-responses-to-weakly-immunogenic-and-lowly-expressed-tumor-antigens
#1
Sabina Kaczanowska, Ann Mary Joseph, Jitao Guo, Alexander K Tsai, Jackline Joy M Lasola, Kenisha Younger, Yuji Zhang, Cruz Velasco Gonzalez, Eduardo Davila
T cell-based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T cell efficacy, including suboptimal T cell receptor (TCR) activation and an immunosuppressive tumor environment. Here we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88-engineered T cells exhibited increased proliferation and expression of effector and co-stimulatory molecules in a tumor antigen-dependent manner...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29053133/-ophthalmic-disorders-as-a-manifestation-of-parkinson-s-disease
#2
N B Chesnokova, T A Pavlenko, M V Ugrumov
Parkinson's disease is a severe neurodegenerative disease accompanied with the degeneration of dopaminergic neurons in the central and peripheral nervous system. The diagnosis of Parkinson's disease can still be made only on the stage of irreversible and nearly total degeneration of the nigrostriatum dopaminergic system and exhaustion of brain compensatory mechanisms that explains the low efficacy of therapy. Ophthalmic pathology is one of the nonmotor symptoms of Parkinson's disease. This can be explained firstly by the fact that eye is a 'peripheral part of brain' and secondly by the involvement of dopaminergic neurons (dopamine-producing cells) that are subject to the selective degeneration during Parkinson's disease in the regulation of visual function in the eye and brain...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/29051561/magt1-mediated-disturbance-of-mg-2-homeostasis-lead-to-exhausted-of-hbv-infected-nk-and-cd8-t-cells
#3
Bo Diao, Xiaoyong Huang, Shen Guo, Chengying Yang, Guosong Liu, Yongwen Chen, Yuzhang Wu
The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium ([Mg(2+)]i) levels. It has been shown that MAGT1 was involved in the disorder in Mg(2+) homeostasis after Epstein-Barr virus (EBV) infection. Here, we identified the effects of MAGT1-mediated disturbance of Mg(2+) homeostasis on chronic hepatitis B virus (HBV)-infected natural killer (NK) and CD8(+) T cells. The expression of MAGT1 was gradually decreased with the increase of infected time in CD8(+) T cells, but not with that in NK cells, of the patients...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29045899/early-transcriptional-divergence-marks-virus-specific-primary-human-cd8-t-cells-in-chronic-versus-acute-infection
#4
David Wolski, Peter K Foote, Diana Y Chen, Lia L Lewis-Ximenez, Catherine Fauvelle, Jasneet Aneja, Andreas Walker, Pierre Tonnerre, Almudena Torres-Cornejo, Daniel Kvistad, Sabrina Imam, Michael T Waring, Damien C Tully, Todd M Allen, Raymond T Chung, Jörg Timm, W Nicholas Haining, Arthur Y Kim, Thomas F Baumert, Georg M Lauer
Distinct molecular pathways govern the differentiation of CD8(+) effector T cells into memory or exhausted T cells during acute and chronic viral infection, but these are not well studied in humans. Here, we employed an integrative systems immunology approach to identify transcriptional commonalities and differences between virus-specific CD8(+) T cells from patients with persistent and spontaneously resolving hepatitis C virus (HCV) infection during the acute phase. We observed dysregulation of metabolic processes during early persistent infection that was linked to changes in expression of genes related to nucleosomal regulation of transcription, T cell differentiation, and the inflammatory response and correlated with subject age, sex, and the presence of HCV-specific CD4(+) T cell populations...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29040163/adipose-tissue-is-enriched-for-activated-and-late-differentiated-cd8-t-cells-and-shows-distinct-cd8-receptor-usage-compared-to-blood-in-hiv-infected-persons
#5
John R Koethe, Wyatt McDonnell, Arion Kennedy, Chike O Abana, Mark Pilkinton, Ian Setliff, Ivelin Georgiev, Louise Barnett, Cindy C Hager, Rita Smith, Spyros A Kalams, Alyssa Hasty, Simon Mallal
BACKGROUND: Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially pro-inflammatory T cell populations in adipose tissue among persons on long-term antiretroviral therapy, and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population. METHODS: We recruited 10 HIV-infected, overweight and obese adults on efavirenz, tenofovir, and emtricitabine for >4 years with consistent viral suppression...
October 14, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29035687/acute-glutamine-ingestion-modulates-lymphocytic-responses-to-exhaustive-exercise-in-the-heat
#6
Chen Zheng, Xiang-Ke Chen, Yue Zhou
The purpose of this study was to determine if acute intake of glutamine modulates homeostatic, hematologic, immune, and inflammatory responses to exhaustive exercise in the heat. Thirteen healthy untrained young men participated in this randomized, double-blind, placebo-controlled, crossover study. They served as their own control and completed two trials of treadmill exercise at 40% VO2max to exhaustion in a hot environment (38.0 ± 1.0 °C, 60.0 ± 5.0 % relative humidity, and 20.8% oxygen) following placebo (PLA) and glutamine (GLN) consumption...
October 16, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/29033936/coinhibitory-receptor-expression-and-immune-checkpoint-blockade-maintaining-a-balance-in-cd8-t-cell-responses-to-chronic-viral-infections-and-cancer
#7
REVIEW
Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi
In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29032101/mitochondrial-activity-in-t-cells
#8
REVIEW
Gabriela Desdín-Micó, Gonzalo Soto-Heredero, María Mittelbrunn
Mitochondria fulfill important and diverse roles during the different stages of T cell adaptive responses. Here we discuss the role of the mitochondria in T cells from the initial steps of activation at the immune synapse to their participation in memory responses and T cell exhaustion. Mitochondria are relocated to the immune synapse in order to supply local ATP and to aid calcium signaling. During expansion and proliferation, mitochondrial reactive oxygen species drive proliferation. Aerobic glycolysis, glutaminolysis and fatty acid oxidation regulate the program of differentiation into effector or regulatory T cell subsets, and mitochondrial remodeling proteins are required for the long-lasting phenotype of memory cells...
October 12, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29031786/differentiation-and-protective-capacity-of-virus-specific-cd8-t-cells-suggest-murine-norovirus-persistence-in-an-immune-privileged-enteric-niche
#9
Vesselin T Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L Cosma, Laurence C Eisenlohr, Timothy J Nice, Herbert W Virgin, E John Wherry
Noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. We used genetically engineered strains of mouse norovirus (MNV) to investigate CD8(+) T cell differentiation during chronic infection. We found that chronic infection drove MNV-specific tissue-resident memory (Trm) CD8(+) T cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus with only limited evidence of exhaustion...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29029951/intrahepatic-v%C3%AE-9v%C3%AE-2-t-cells-from-hcv-infected-patients-show-an-exhausted-phenotype-but-can-inhibit-hcv-replication
#10
E Cimini, V Bordoni, A Sacchi, U Visco-Comandini, M Montalbano, C Taibi, R Casetti, E Lalle, G D'Offizi, M R Capobianchi, C Agrati
Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction. Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCV(pos)) and in HCV-negative (HCV(neg)) subjects. Phenotypic and functional analysis was performed by flow cytometry...
October 10, 2017: Virus Research
https://www.readbyqxmd.com/read/29027218/cell-death-and-immunity-in-cancer-from-danger-signals-to-mimicry-of-pathogen-defense-responses
#11
REVIEW
Abhishek D Garg, Patrizia Agostinis
The immunogenicity of cancer cells is an emerging determinant of anti-cancer immunotherapy. Beyond developing immunostimulatory regimens like dendritic cell-based vaccines, immune-checkpoint blockers, and adoptive T-cell transfer, investigators are beginning to focus on the immunobiology of dying cancer cells and its relevance for the success of anticancer immunotherapies. It is currently accepted that cancer cells may die in response to anti-cancer therapies through regulated cell death programs, which may either repress or increase their immunogenic potential...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29023417/control-of-nk-cell-activation-by-immune-checkpoint-molecules
#12
REVIEW
Asma Beldi-Ferchiou, Sophie Caillat-Zucman
The development of cancer and chronic infections is facilitated by many subversion mechanisms, among which enhanced expression of immune checkpoints molecules, such as programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), on exhausted T cells. Recently, immune checkpoint inhibitors have shown remarkable efficiency in the treatment of a number of cancers. However, expression of immune checkpoints on natural killer (NK) cells and its functional consequences on NK cell effector functions are much less explored...
October 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29021092/t-cells-and-their-cytokine-production-the-anti-inflammatory-and-immunosuppressive-effects-of-strenuous-exercise
#13
REVIEW
David M Shaw, Fabrice Merien, Andrea Braakhuis, Deborah Dulson
Strenuous exercise bouts and heavy training are associated with a heightened anti-inflammatory state and a transient suppression of several immune components. In turn, many athletes are susceptible to illness, particularly upper respiratory symptoms (e.g. cough, sore throat, running nose). T-lymphocytes (T-cells) are important for orchestrating the immune response and can be categorised into subsets according to their phenotypical characteristics resulting from polarisation (i.e. type-1, type-2 and regulatory T-cells)...
October 8, 2017: Cytokine
https://www.readbyqxmd.com/read/29016938/preclinical-investigation-of-gene-mediated-cytotoxic-immunotherapy-and-checkpoint-blockade-in-glioblastoma
#14
Maria-Carmela Speranza, Carmela Passaro, Franz Ricklefs, Kazue Kasai, Sarah R Klein, Hiroshi Nakashima, Johanna K Kaufmann, Abdul-Kareem Ahmed, Michal O Nowicki, Prisca Obi, Agnieszka Bronisz, Estuardo Aguilar-Cordova, Laura K Aguilar, Brian W Guzik, Xandra Breakefield, Ralph Weissleder, Gordon J Freeman, David A Reardon, Patrick Wen, E Antonio Chiocca, Sean E Lawler
Background: Combined immunotherapy approaches are promising cancer treatments. We evaluated anti-PD-1 treatment combined with Gene-mediated cytotoxic immunotherapy (GMCI) performed by intratumoral injection of a prodrug metabolizing non-replicating adenovirus (AdV-tk), providing insitu chemotherapy and immune stimulation. Methods: The effects of GMCI on PD-L1 expression in glioblastoma were investigated in vitro and in vivo. The efficacy of the combination was investigated in two syngeneic mouse glioblastoma models (GL261 and CT-2A)...
July 24, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29016879/agonist-ox40-immunotherapy-improves-survival-in-glioma-bearing-mice-and-is-complementary-with-vaccination-with-irradiated-gm-csf-expressing-tumor-cells
#15
Nusrat Jahan, Hammad Talat, William T Curry
Background: Glioma immunotherapy is an active area of clinical investigation. Glioma-associated immunosuppression remains an obstacle to efficacious immunotherapy, and combination approaches are likely necessary for durable success. OX40 is a member of the tumor necrosis factor receptor superfamily that is upregulated on activated lymphocytes, ligation of which results in enhanced activity and may be active against cancer. We sought to confirm the efficacy of agonist anti-OX40 immunotherapy against glioma and hypothesized that it is complementary with irradiated whole tumor cell vaccination...
July 7, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28994661/vitamin-d-supplementation-decreases-immune-activation-and-exhaustion-in-hiv-1-infected-youth
#16
Allison Ross Eckard, Mary Ann O'Riordan, Julia C Rosebush, Seungeun Thera Lee, Jakob G Habib, Joshua H Ruff, Danielle Labbato, Julie E Daniels, Monika Uribe-Leitz, Vin Tangpricha, Ann Chahroudi, Grace A McComsey
BACKGROUND: Heightened immune activation and exhaustion drive HIV disease progression and co-morbidities. Vitamin D has pleiotropic immunomodulatory effects, but little is known about the effects of supplementation in HIV. Our study investigates changes in immune activation and exhaustion markers after 12 months of supplementation in virologically-suppressed HIV-infected youth with vitamin D insufficiency. METHODS: This is a randomized, active-control, double-blind trial investigating with 3 different vitamin D3 doses [18,000 (standard/active-control dose), 60,000 (moderate dose) and 120,000 IU/monthly (high dose)] in 8-26 year old HIV-infected youth on combination antiretroviral therapy with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations ≤30 ng/mL...
October 10, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28993768/cd30-is-dispensable-for-t-cell-responses-to-influenza-virus-and-lymphocytic-choriomeningitis-virus-clone-13-but-contributes-to-age-associated-t-cell-expansion-in-mice
#17
Angela C Zhou, Laura M Snell, Michael E Wortzman, Tania H Watts
CD30 is a tumor necrosis factor receptor (TNFR) family member whose expression is associated with Hodgkin's disease, anaplastic large cell lymphomas, and other T and B lymphoproliferative disorders in humans. A limited number of studies have assessed the physiological role of CD30/CD30 ligand interactions in control of infection in mice. Here, we assess the role of CD30 in T-cell immunity to acute influenza and chronic lymphocytic choriomeningitis virus (LCMV) clone 13 infection, two viral infections in which other members of the TNFR superfamily are important for T-cell responses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28985739/a-lipidated-peptide-of-mycobacterium-tuberculosis-resuscitates-the-protective-efficacy-of-bcg-vaccine-by-evoking-memory-t-cell-immunity
#18
Pradeep K Rai, Sathi Babu Chodisetti, Weiguang Zeng, Sajid Nadeem, Sudeep K Maurya, Susanta Pahari, Ashok K Janmeja, David C Jackson, Javed N Agrewala
BACKGROUND: The current BCG vaccine induces only short-term protection against Mycobacterium tuberculosis (Mtb), suggesting its failure to generate long-lasting memory T cells. Previously, we have demonstrated that a self-adjuvanting peptide of Mtb (L91), successfully generated enduring memory Th1 cells. Consequently, we investigated if L91 was able to recuperate BCG potency in perpetuating the generation of memory T cells and protection against Mtb infected mice. METHODS: In the present study, we evaluated the potency of a self adjuvanting Mtb peptide vaccine L91 in invigorating BCG immune response against Mtb in mice...
October 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28985469/programmed-cell-death-protein-ligand-1-silencing-with-polyethylenimine-dermatan-sulfate-complex-for-dual-inhibition-of-melanoma-growth
#19
Gijung Kwak, Dongkyu Kim, Gi-Hoon Nam, Sun Young Wang, In-San Kim, Sun Hwa Kim, Ick-Chan Kwon, Yoon Yeo
Programmed cell death protein-1 (PD-1) is a prominent immune checkpoint receptor interacting with its ligand, programmed cell death protein ligand-1 (PD-L1, B7-H1). The PD-1/PD-L1 interaction induces functional exhaustion of tumor-reactive cytotoxic T cells and, thus, interferes with antitumor T-cell immunity. In addition, PD-1/PD-L1 interaction promotes tumorigenesis via the mTOR signaling pathway in a group of cancers including melanoma. Based on the dual functions of PD-1/PD-L1 interactions in tumor progression, we hypothesize that siRNA targeting PD-L1 (siPD-L1) will suppress melanoma growth, acting on both immune checkpoint and intrinsic tumorigenesis pathways...
October 12, 2017: ACS Nano
https://www.readbyqxmd.com/read/28981470/telomere-dynamics-in-immune-senescence-and-exhaustion-triggered-by-chronic-viral-infection
#20
REVIEW
Marcia Bellon, Christophe Nicot
The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics...
October 5, 2017: Viruses
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