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Lymphocyte exhaustion

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https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#1
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/29296862/brafv600e-accelerates-disease-progression-and-enhances-immune-suppression-in-a-mouse-model-of-b-cell-leukemia
#2
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/29278684/isolation-of-human-lymphocytes-with-high-yield-and-viability-from-the-gastrointestinal-and-female-reproductive-tract-of-a-humanized-drag-mouse
#3
Atef Allam, Kristina K Peachman, Rodrigo Aguilera-Olvera, Sofia Casares, Mangala Rao
The mucosal tissues of the gut and female reproductive tract (FRT) are susceptible to pathogen infections including bacteria, viruses, and parasites, and are also the targets for immune disorders such as Crohn's disease, inflammatory bowel disease (IBD), and many types of cancers. However, the role of the mucosal immune cells to control these diseases is largely unknown. The limited availability of human mucosal biopsy tissue and the low number of cells that can be isolated from these tissues hampers the characterization of the phenotype and function of human mucosal immune cell subsets...
December 23, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29276179/cd4-t-cells-are-exhausted-and-show-functional-defects-in-chronic-lymphocytic-leukemia
#4
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/29259496/immunosenescence-in-aging-between-immune-cells-depletion-and-cytokines-up-regulation
#5
REVIEW
Maria Teresa Ventura, Marco Casciaro, Sebastiano Gangemi, Rosalba Buquicchio
Background: The immunosenescence is a relatively recent chapter, correlated with the linear extension of the average life began in the nineteenth century and still in progress. The most important feature of immunosenescence is the accumulation in the "immunological space" of memory and effector cells as a result of the stimulation caused by repeated clinical and subclinical infections and by continuous exposure to antigens (inhalant allergens, food, etc.). This state of chronic inflammation that characterizes senescence has a significant impact on survival and fragility...
2017: Clinical and Molecular Allergy: CMA
https://www.readbyqxmd.com/read/29250072/alterations-in-b-cell-compartment-correlate-with-poor-neutralization-response-and-disease-progression-in-hiv-1-infected-children
#6
Heena Aggarwal, Lubina Khan, Omkar Chaudhary, Sanjeev Kumar, Muzamil Ashraf Makhdoomi, Ravinder Singh, Kanika Sharma, Nitesh Mishra, Rakesh Lodha, Maddur Srinivas, Bimal Kumar Das, Sushil Kumar Kabra, Kalpana Luthra
Several B cell defects are reported in HIV-1 infected individuals including variation in B cell subsets, polyclonal B cell activation and exhaustion, with broadly neutralizing antibodies elicited in less than 10-20% of the infected population. HIV-1 disease progression is faster in children than adults. B Lymphocyte Stimulator (BLyS), expressed on dendritic cells (DCs), is a key regulator of B cell homeostasis. Understanding how DCs influence B cell phenotype and functionality (viral neutralization), thereby HIV-1 disease outcome in infected children, is important to develop interventional strategies for restoration of B cell function...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29246443/transcription-factor-irf4-promotes-cd8-t-cell-exhaustion-and-limits-the-development-of-memory-like-t-cells-during-chronic-infection
#7
Kevin Man, Sarah S Gabriel, Yang Liao, Renee Gloury, Simon Preston, Darren C Henstridge, Marc Pellegrini, Dietmar Zehn, Friederike Berberich-Siebelt, Mark A Febbraio, Wei Shi, Axel Kallies
During chronic stimulation, CD8+ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1...
December 11, 2017: Immunity
https://www.readbyqxmd.com/read/29245183/increased-expression-and-modulated-regulatory-activity-of-co-inhibitory-receptors-pd-1-tigit-and-tim-3-in-lymphocytes-of-systemic-sclerosis-patients
#8
Michelle Fleury, Anna C Belkina, Elizabeth A Proctor, Christopher Zammitti, Robert W Simms, Douglas A Lauffenburger, Jennifer E Snyder-Cappione, Robert Lafyatis, Hans Dooms
OBJECTIVE: Immune dysfunction is an important component of the disease process underlying Systemic Sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. Here, we measured the expression and function of the co-inhibitory receptors (co-IRs) PD-1, TIGIT, TIM-3, and LAG-3 in lymphocyte subsets from the peripheral blood of SSc patients. METHODS: Co-IR expression levels on immune cell subsets were analyzed using a 16-color flow cytometry panel...
December 15, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29213079/human-cd26high-t-cells-elicit-tumor-immunity-against-multiple-malignancies-via-enhanced-migration-and-persistence
#9
Stefanie R Bailey, Michelle H Nelson, Kinga Majchrzak, Jacob S Bowers, Megan M Wyatt, Aubrey S Smith, Lillian R Neal, Keisuke Shirai, Carmine Carpenito, Carl H June, Michael J Zilliox, Chrystal M Paulos
CD8+ T lymphocytes mediate potent immune responses against tumor, but the role of human CD4+ T cell subsets in cancer immunotherapy remains ill-defined. Herein, we exhibit that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26neg T cells possess a regulatory phenotype, CD26int T cells are mainly naive and CD26high T cells appear terminally differentiated and exhausted. Paradoxically, CD26high T cells persist in and regress multiple solid tumors following adoptive cell transfer...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29198314/t-cell-resistance-to-activation-by-dendritic-cells-requires-long-term-culture-in-simulated-microgravity
#10
Jillian H Bradley, Rachel Stein, Brad Randolph, Emily Molina, Jennifer P Arnold, Randal K Gregg
Immune impairment mediated by microgravity threatens the success of space exploration requiring long-duration spaceflight. The cells of most concern, T lymphocytes, coordinate the host response against microbial and cancerous challenges leading to elimination and long-term protection. T cells are activated upon recognition of specific microbial peptides bound on the surface of antigen presenting cells, such as dendritic cells (DC). Subsequently, this engagement results in T cell proliferation and differentiation into effector T cells driven by autocrine interleukin-2 (IL-2) and other cytokines...
November 2017: Life Sciences in Space Research
https://www.readbyqxmd.com/read/29196449/sustained-t-follicular-helper-cell-response-is-essential-for-control-of-chronic-viral-infection
#11
Ute Greczmiel, Nike Julia Kräutler, Alessandro Pedrioli, Ilka Bartsch, Paola Agnellini, Gregor Bedenikovic, James Harker, Kirsten Richter, Annette Oxenius
During chronic viral infections, both CD8 and CD4 T cell responses are functionally compromised. Alongside exhaustion of CD8 T cells during chronic viral infections, it has also been documented that the CD4 T cells have an increased propensity to differentiate toward CXCR5+ T follicular helper cell (TFH) lineage. Whether these TFH cells contribute to the immune response to chronic viral infection has remained unclear. Using chronic lymphocytic choriomeningitis virus (LCMV) infection in conjunction with an in vivo system where TFH cells can be conditionally ablated, we have established that these TFH cells do in fact play an important protective function...
December 1, 2017: Science Immunology
https://www.readbyqxmd.com/read/29176992/immunosenescence-in-persons-with-spinal-cord-injury-in-relation-to-urinary-tract-infections-a-cross-sectional-study
#12
David Pavlicek, Jörg Krebs, Simona Capossela, Alessandro Bertolo, Britta Engelhardt, Jürgen Pannek, Jivko Stoyanov
Background: Individuals with a spinal cord injury (SCI), despite specialized rehabilitation and good health care, have a reduced life expectancy. Infectious diseases, such as pneumonias, infected pressure sores and urinary tract infections (UTI) have been identified as the leading causes of mortality. We hypothesise that a premature onset of immune frailty occurs in SCI, possibly caused also by recurrent urinary tract infections.A cross sectional study was performed comparing blood and urine samples between able bodied controls (n = 84) and persons with spinal cord injury (n = 85)...
2017: Immunity & Ageing: I & A
https://www.readbyqxmd.com/read/29164800/the-generation-of-human-%C3%AE-%C3%AE-t-cell-derived-induced-pluripotent-stem-cells-from-whole-peripheral-blood-mononuclear-cell-culture
#13
Daisuke Watanabe, Michiyo Koyanagi-Aoi, Mariko Taniguchi-Ikeda, Yukiko Yoshida, Takeshi Azuma, Takashi Aoi
γδT cells constitute a small proportion of lymphocytes in peripheral blood. Unlike αβT cells, the anti-tumor activities are exerted through several different pathways in a MHC-unrestricted manner. Thus, immunotherapy using γδT cells is considered to be effective for various types of cancer. Occasionally, however, ex vivo expanded cells are not as effective as expected due to cell exhaustion. To overcome the issue of T-cell exhaustion, researchers have generated induced pluripotent stem cells (iPSCs) that harbor the same T-cell receptor (TCR) genes as their original T-cells, which provide nearly limitless sources for antigen-specific cytotoxic T lymphocytes (CTLs)...
January 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29163789/prostaglandin-e2-and-pd-1-mediated-inhibition-of-antitumor-ctl-responses-in-the-human-tumor-microenvironment
#14
Jie Miao, Xu Lu, Yuefeng Hu, Chunmei Piao, Xuan Wu, Xuesong Liu, Caiting Huang, Yue Wang, Dan Li, Jingwei Liu
Accumulating evidence indicates that inflammation plays a critical role in cancer development; however, mechanisms of immunosuppression hinder productive anti-tumor immunity to limit immunopathology. Tumor-specific cytotoxic T lymphocyte (CTL) dysfunction or exhaustion by upregulating inhibitory receptors such as programmed cell death 1 (PD-1) in tumor-bearing hosts is one such mechanism. Identification and blockade of the pathways that induce CTL dysfunction has been shown to partially restore CTL function in tumor-bearing hosts...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29140111/purging-exhausted-virus-specific-cd8-t-cell-phenotypes-by-somatic-cell-reprogramming
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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