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Lymphocyte exhaustion

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https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#1
Joshua Chan, Patrick Y Kim, Emiko Kranz, Yoshiko Nagaoka, YooJin Lee, Jing Wen, Heidi J Elsaesser, Meng Qin, David G Brooks, Gene-Errol Ringpis, Irvin S Y Chen, Masakazu Kamata
Cytotoxic T cells are critical in controlling virus infections. However, continuous antigen stimulation and negative regulatory factors cause CD8 T cells to enter a dysfunctional state (T cell exhaustion), resulting in viral persistence. We hypothesized that the exhausted T cell state could be molecularly rejuvenated using a somatic cell reprogramming technology, which is technically able to convert any types of cells to induced pluripotent stem cells (iPSCs), to regenerate functional T cells capable of purging chronic infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29137886/diesel-exhaust-inhalation-exposure-induces-pulmonary-arterial-hypertension-in-mice
#2
Jing Liu, Xiaoqing Ye, Dapeng Ji, Xiaofei Zhou, Cong Qiu, Weiping Liu, Luyang Yu
Diesel exhaust (DE) is one of the main sources of urban air pollution. An increasing number of evidence showed the association of air pollution with cardiovascular diseases. Pulmonary arterial hypertension (PAH) is one of the most disastrous vascular diseases, which results in right ventricular failure and death. However, the relationship of DE inhalation exposure with PAH is still unknown. In this study, male adult mice were exposed by inhalation to filtered ambient air (negative control), 10% O2 hypoxia (PAH-phenotype positive control), 350 μg/m(3) particulate matter whole DE, or the combination of DE and hypoxic condition...
November 11, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29121254/impact-of-donor-and-recipient-human-cytomegalovirus-status-on-kidney-transplantation
#3
Maciej Zielinski, Agnieszka Tarasewicz, Hanna Zielinska, Magdalena Jankowska, Grazyna Moszkowska, Alicja Debska-Slizien, Boleslaw Rutkowski, Piotr Trzonkowski
Human cytomegalovirus (HCMV) is considered to be a major pathogen that affects the outcome of solid organ transplantation. Both recipient and donor may be HCMV positive, therefore HCMV reinfection is possible after transplantation. However, little is known how cytomegalovirus transmitted from an infected donor to an infected recipient modulates the recipient's already suppressed immunity, and what the clinical consequences are. To investigate these issues, 52 kidney recipients were followed up for two years after transplantation...
November 7, 2017: International Immunology
https://www.readbyqxmd.com/read/29118007/pd-1-expression-and-clinical-pd-1-blockade-in-b-cell-lymphomas
#4
Zijun Y Xu-Monette, Jianfeng Zhou, Ken H Young
PD-1 blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/PD-L1 expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1(+) tumor-infiltrating T cells, 9p24 genetic alteration and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORR) of 65-87% and durable disease control in phase I/II clinical trials...
November 8, 2017: Blood
https://www.readbyqxmd.com/read/29084057/evaluation-of-pd1-pdl1-expression-and-their-clinicopathologic-association-in-ebv-associated-lymphoproliferative-disorders-in-nonimmunosuppressed-patients
#5
Ling Guo, Juraj Bodo, Lisa Durkin, Eric D Hsi
Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPD)/lymphomas in nonimmunosuppressed patients represent a unique entity and have been proposed to be related to immune senescence. Engagement of programmed cell death 1 (PD1) by its ligand programmed death ligand 1 (PDL1) inhibits T-cell activation, and leads to T-cell exhaustion. In clinical trials, therapeutic antibodies that block the PD1-PDL1 axis have shown promising therapeutic activity in certain types of lymphomas. Although PD1/PDL1 has been extensively studied in variety of lymphomas, there are few reports characterizing their expression in EBV-positive LPD...
October 27, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29079339/exhaustion-of-t-lymphocytes-in-the-tumor-microenvironment-significance-and-effective-mechanisms
#6
REVIEW
Mohammad Davoodzadeh Gholami, Gholam Ali Kardar, Yousef Saeedi, Sahel Heydari, Johan Garssen, Reza Falak
T lymphocytes play crucial roles in adaptive immune responses to tumors. However, due to different tolerance mechanisms and inhibitory effects of the tumor microenvironment (TME) on T cells, responses to tumors are insufficient. In fact, cellular and molecular suppressive mechanisms repress T cell responses in the TME, resulting in senescent, anergic and exhausted lymphocytes. Exhaustion is a poor responsive status of T cells, with up-regulated expression of inhibitory receptors, decreased production of effective cytokines, and reduced cytotoxic activity...
October 10, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29071472/immune-interventions-to-eliminate-the-hiv-reservoir
#7
Denise C Hsu, Jintanat Ananworanich
Inducing HIV remission is a monumental challenge. A potential strategy is the "kick and kill" approach where latently infected cells are first activated to express viral proteins and then eliminated through cytopathic effects of HIV or immune-mediated killing. However, pre-existing immune responses to HIV cannot eradicate HIV infection due to the presence of escape variants, inadequate magnitude, and breadth of responses as well as immune exhaustion. The two major approaches to boost immune-mediated elimination of infected cells include enhancing cytotoxic T lymphocyte mediated killing and harnessing antibodies to eliminate HIV...
October 26, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/29069777/small-molecule-inhibitors-of-pd-1-pd-l1-immune-checkpoint-alleviate-the-pd-l1-induced-exhaustion-of-t-cells
#8
Lukasz Skalniak, Krzysztof M Zak, Katarzyna Guzik, Katarzyna Magiera, Bogdan Musielak, Magdalena Pachota, Bozena Szelazek, Justyna Kocik, Przemyslaw Grudnik, Marcin Tomala, Sylwia Krzanik, Krzysztof Pyrc, Alexander Dömling, Grzegorz Dubin, Tad A Holak
Antibodies targeting the PD-1/PD-L1 immune checkpoint achieved spectacular success in anticancer therapy in the recent years. In contrast, no small molecules with cellular activity have been reported so far. Here we provide evidence that small molecules are capable of alleviating the PD-1/PD-L1 immune checkpoint-mediated exhaustion of Jurkat T-lymphocytes. The two optimized small-molecule inhibitors of the PD-1/PD-L1 interaction, BMS-1001 and BMS-1166, developed by Bristol-Myers Squibb, bind to human PD-L1 and block its interaction with PD-1, when tested on isolated proteins...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29069649/the-systemic-activation-of-programmed-death-1-pd-l1-axis-protects-systemic-lupus-erythematosus-model-from-nephritis
#9
Wenjun Liao, Hua Zheng, Sha Wu, Yanmei Zhang, Wei Wang, Zili Zhang, Chenfei Zhou, Hongjun Wu, Jie Min
BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by abnormal activated T cells, autoreactive B cells, and massive cytokines. The CD4+ T cells determined B-cells differentiation and cytokines production. The programmed death 1 (PD-1) is the checkpoint immunoinhibitory receptor of activated T cells, and its engagement could exhaust T cells. In this study, we investigated the role of PD-1 systemic engagement with PD-L1-Ig in lupus-like nephritis in SLE mice. METHODS: The murine PD-L1-Ig was injected into SLE-prone mice...
October 26, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29066514/cd39-expression-defines-cell-exhaustion-in-tumor-infiltrating-cd8-t-cells
#10
Fernando P Canale, Maria C Ramello, Nicolas Núñez, Cintia L Araujo Furlan, Sabrina N Bossio, Melisa Gorosito Serrán, Jimena Tosello Boari, Andrés Del Castillo, Marta Ledesma, Christine Sedlik, Eliane Piaggio, Adriana Gruppi, Eva V Acosta Rodríguez, Carolina L Montes
The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ecto-nucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL-2 and expression of co-inhibitory receptors...
October 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/29044000/observation-on-shenqi-fuzheng-injection-combined-with-cefoxitin-sodium-after-cesarean-section
#11
Jingge Chen, Yumin Cheng, Xinxiang Ma, Yuanyuan Cao
This paper aims to observe the effect of Shenqi Fuzheng Injection combined with cefoxitin sodium after cesarean section. Clinical data of 126 puerperae were retrospectively analyzed. They randomized into control group and treatment group, and there were 63 cases in each group. Patients in control group were given Cefoxitin Sodium treatment. And patients in treatment group were given Shenqi Fuzheng Injection on the basis of control group. After 7 days of treatment, the clinical curative effect of the two groups was observed and compared...
July 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29035687/acute-glutamine-ingestion-modulates-lymphocytic-responses-to-exhaustive-exercise-in-the-heat
#12
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
#13
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/29023417/control-of-nk-cell-activation-by-immune-checkpoint-molecules
#14
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
#15
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/29016879/agonist-ox40-immunotherapy-improves-survival-in-glioma-bearing-mice-and-is-complementary-with-vaccination-with-irradiated-gm-csf-expressing-tumor-cells
#16
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/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/28978072/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#18
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28959265/novel-method-for-high-throughput-full-length-ighv-d-j-sequencing-of-the-immune-repertoire-from-bulk-b-cells-with-single-cell-resolution
#19
Stefano Vergani, Ilya Korsunsky, Andrea Nicola Mazzarello, Gerardo Ferrer, Nicholas Chiorazzi, Davide Bagnara
Efficient and accurate high-throughput DNA sequencing of the adaptive immune receptor repertoire (AIRR) is necessary to study immune diversity in healthy subjects and disease-related conditions. The high complexity and diversity of the AIRR coupled with the limited amount of starting material, which can compromise identification of the full biological diversity makes such sequencing particularly challenging. AIRR sequencing protocols often fail to fully capture the sampled AIRR diversity, especially for samples containing restricted numbers of B lymphocytes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28955243/the-effect-of-a-100-km-ultra-marathon-under-freezing-conditions-on-selected-immunological-and-hematological-parameters
#20
Alena Žákovská, Beat Knechtle, Daniela Chlíbková, Marie Miličková, Thomas Rosemann, Pantelis T Nikolaidis
Although moderate exercise is beneficial for the human body and its immune system, exhaustive ultra-endurance performance in cold conditions might be harmful. The aim of this study was to examine the effect of a 100-km ultra-marathon under cold conditions (temperatures from -1°C to +1°C) on selected immunological, biochemical and hematological parameters. Participants were 15 runners (12 men and three women, age 40.3 ± 9.7 years, body mass 67.3 ± 9.0 kg and body height 1.74 ± 0.10 m, mean ± standard deviation)...
2017: Frontiers in Physiology
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