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CD8 tolerance

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https://www.readbyqxmd.com/read/29352109/role-of-b-and-t-lymphocyte-attenuator-in-renal-transplant-recipients-with-biopsy-proven-acute-rejection
#1
Zijie Wang, Haiwei Yang, Xuzhong Liu, Jingying Zhang, Zhijian Han, Jun Tao, Chunchun Zhao, Xiaobin Ju, Ruoyun Tan, Min Gu
BACKGROUND Acute rejection is a common predisposing cause of allograft dysfunction in kidney transplantation. Recently, the B and T lymphocyte attenuator (BTLA)/herpes virus entry mediator (HVEM)/lymphotoxin (LIGHT)/CD160 pathway was found to be potentially involved in the regulation of T cell activation. This could mean that this pathway is involved in graft rejection in kidney transplantation; the present study aimed to explore this possibility. MATERIAL AND METHODS The expression of BTLA, HVEM, LIGHT and CD160 on peripheral CD4+, CD8+ and CD19+ lymphocytes were analyzed by flow cytometry in recipients with biopsy-proven acute rejection (BPAR) or stable allograft function, as well as in healthy volunteers...
January 20, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29344157/expression-and-clinical-significance-of-programmed-death-1-on-lymphocytes-and-programmed-death-ligand-1-on-monocytes-in-the-peripheral-blood-of-patients-with-cervical-cancer
#2
Ying Zhang, Weipei Zhu, Xueguang Zhang, Qiuxia Qu, Liyuan Zhang
The programmed death-1 (PD-1) signaling pathway serves a critical role in immune regulation and tolerance by suppressing the activation and proliferation of T cells. The aim of the present study was to investigate the effect of PD-1 and programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40 patients with CIN and 66 newly diagnosed cervical cancer patients were recruited. The expression level of PD-1 expression on peripheral cluster of differentiation (CD)4+ and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29338160/higher-activities-of-hepatic-versus-splenic-cd8-t-cells-in-responses-to-adoptive-t-cell-therapy-and-vaccination-of-b6-mice-with-mhc-class-1-binding-antigen
#3
Mohamed Labib Salem, Randa E El Naggar, Sabry A El Naggar, Maysa A Mobasher, Mohamed H Mahmoud, Gamal Badr
The liver has unique microenvironment which is known to induce tolerance of cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in persistence of infection of the liver by the hepatitis B and C viruses. However, under some conditions, functional immune responses can be elicited in the liver in particular to show preferential retention of activated CD8+ T cells. It is not clear whether this retention depends on the type of the exogenous immunostimulatory or the endogenous innate immune cells...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29306503/a-mouse-model-with-age-dependent-immune-response-and-immune-tolerance-for-hbv-infection
#4
Xuerui Yi, Youcheng Yuan, Na Li, Lu Yi, Cuiling Wang, Ying Qi, Liang Gong, Guangze Liu, Xiangping Kong
BACKGROUND: Viral clearance of human HBV infection largely depends on the age of exposure. Thus, a mouse model with age-dependent immune response and immune-tolerance for HBV infection was established. METHODS: HBVRag1 mice were generated by crossing Rag1-/- mice with HBV-Tg mice. Following adoptive transfer of splenocytes adult (8-9 weeks old) and young (3 weeks old) HBVRag1 mice were named as HBVRag-ReA and HBVRag-ReY mice respectively. The biochemical parameters that were associated with viral load and immune function, as well as the histological evaluation of the liver tissues between the two mouse models were detected...
January 3, 2018: Vaccine
https://www.readbyqxmd.com/read/29301826/p53-reactive-t-cells-are-associated-with-clinical-benefit-in-patients-with-platinum-resistant-epithelial-ovarian-cancer-after-treatment-with-a-p53-vaccine-and-gemcitabine-chemotherapy
#5
Nicola R Hardwick, Paul Frankel, Christopher Ruel, Julie Kilpatrick, Weimin Tsai, Ferdynand Kos, Teodora I Kaltcheva, Lucille Leong, Robert Morgan, Vincent Chung, Raechelle Tinsley, Melissa Eng, Sharon P Wilczynski, Joshua D I Ellenhorn, Don J Diamond, Mihaela Cristea
PURPOSE: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29300231/long-term-nonhuman-primate-renal-allograft-survival-without-ongoing-immunosuppression-in-recipients-of-delayed-donor-bone-marrow-transplantation
#6
Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Svjetlan Boskovic, Masatoshi Matsunami, Ivy Rosales, Rex N Smith, Robert B Colvin, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We have previously reported successful induction of renal allograft tolerance in nonhuman primates (NHP) following an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-CD154 and anti-CD8 mAbs plus equine ATG (Atgam) and donor bone marrow transplantation (DBMT). Since these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients of deceased donor allografts...
January 4, 2018: Transplantation
https://www.readbyqxmd.com/read/29296867/long-term-control-of-recurrent-or-refractory-viral-infections-after-allogeneic-hsct-with-third-party-virus-specific-t-cells
#7
Barbara Withers, Emily Blyth, Leighton E Clancy, Agnes Yong, Chris Fraser, Jane Burgess, Renee Simms, Rebecca Brown, David Kliman, Ming-Celine Dubosq, David Bishop, Gaurav Sutrave, Chun Kei Kris Ma, Peter J Shaw, Kenneth P Micklethwaite, David J Gottlieb
Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy...
November 14, 2017: Blood Advances
https://www.readbyqxmd.com/read/29285200/activation-of-pge2-ep2-and-pge2-ep4-signaling-pathways-positively-regulate-the-level-of-pd-1-in-infiltrating-cd8-t-cells-in-patients-with-lung-cancer
#8
Jinhong Wang, Li Zhang, Dong Kang, Deguang Yang, Ying Tang
The present study aimed to identify the level of programmed death-1 (PD-1) expression in infiltrating cluster of differentiation (CD)4+ and CD8+ T cells isolated from lung cancer tissues, and investigated whether the level of PD-1 expression may be directly regulated by lung cancer cells via prostaglandin E2 (PGE2)-associated signaling pathways in patients with lung cancer. A total of 75 patients with lung cancer were enrolled in the present study. The percentage of infiltrating CD4+ and CD8+ T cells was determined by flow cytometry...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29282521/engineered-exosomes-emerging-from-muscle-cells-break-immune-tolerance-to-her2-in-transgenic-mice-and-induce-antigen-specific-ctls-upon-challenge-by-human-dendritic-cells
#9
Simona Anticoli, Eleonora Aricò, Claudia Arenaccio, Francesco Manfredi, Chiara Chiozzini, Eleonora Olivetta, Flavia Ferrantelli, Laura Lattanzi, Maria Teresa D'Urso, Enrico Proietti, Maurizio Federico
We recently described a novel biotechnological platform for the production of unrestricted cytotoxic T lymphocyte (CTL) vaccines. It relies on in vivo engineering of exosomes, i.e., nanovesicles constitutively released by all cells, with full-length antigens of choice upon fusion with an exosome-anchoring protein referred to as Nefmut. They are produced upon intramuscular injection of a DNA vector and, when uploaded with a viral tumor antigen, were found to elicit an immune response inhibiting the tumor growth in a model of transplantable tumors...
December 27, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29262323/extracellular-atp-activates-the-nlrp3-inflammasome-and-is-an-early-danger-signal-of-skin-allograft-rejection
#10
Joaquín Amores-Iniesta, Maria Barberà-Cremades, Carlos M Martínez, José A Pons, Beatriz Revilla-Nuin, Laura Martínez-Alarcón, Francesco Di Virgilio, Pascual Parrilla, Alberto Baroja-Mazo, Pablo Pelegrín
Immune cells are equipped with a number of receptors that recognize sterile injury and pathogens. We find that host immune cells release ATP as an inflammatory signal in response to allogeneic transplantation. ATP then acts via a feedback mechanism on the P2X7 channel to activate the NLRP3 inflammasome and subsequently process and release interleukin (IL)-18. This process is a necessary stage in the deleterious Th1 response against allotransplantation via interferon-γ production. Lack of IL-18 resulted in a decrease in graft-infiltrating CD8 cells but an increase in regulatory T cells...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29259578/t-cell-mediated-beta-cell-destruction-autoimmunity-and-alloimmunity-in-the-context-of-type-1-diabetes
#11
REVIEW
Adam L Burrack, Tijana Martinov, Brian T Fife
Type 1 diabetes (T1D) results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29259248/aav-vector-meditated-expression-of-hla-g-reduces-injury-induced-corneal-vascularization-immune-cell-infiltration-and-fibrosis
#12
Matthew L Hirsch, Laura M Conatser, Sara M Smith, Jacklyn H Salmon, Jerry Wu, Nicholas E Buglak, Rich Davis, Brian C Gilger
Over 1.5 million individuals suffer from cornea vascularization due to genetic and/or environmental factors, compromising visual acuity and often resulting in blindness. Current treatments of corneal vascularization are limited in efficacy and elicit undesirable effects including, ironically, vision loss. To develop a safe and effective therapy for corneal vascularization, adeno-associated virus (AAV) gene therapy, exploiting a natural immune tolerance mechanism induced by human leukocyte antigen G (HLA-G), was investigated...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29259116/mixed-signature-of-activation-and-dysfunction-allows-human-decidual-cd8-t-cells-to-provide-both-tolerance-and-immunity
#13
Anita van der Zwan, Kevin Bi, Errol R Norwitz, Ângela C Crespo, Frans H J Claas, Jack L Strominger, Tamara Tilburgs
Understanding how decidual CD8+ T cell (CD8+ dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal-fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8+ dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8+ dT effector responses to maintain tolerance to fetal antigens...
December 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29258717/tolerogenic-ag-plg-nanoparticles-induce-tregs-to-suppress-activated-diabetogenic-cd4-and-cd8-t-cells
#14
Suchitra Prasad, Tobias Neef, Dan Xu, Joseph R Podojil, Daniel R Getts, Lonnie D Shea, Stephen D Miller
Type 1 diabetes (T1D) is mediated by destruction of pancreatic β cells by autoantigen-specific CD4+ and CD8+ T cells, thus the ideal solution for T1D is the restoration of immune tolerance to β cell antigens. We demonstrate the ability of carboxylated 500 nm biodegradable poly(lactide-co-glycolide) (PLG) nanoparticles PLG nanoparticles (either surface coupled with or encapsulating the cognate diabetogenic peptides) to rapidly and efficiently restore tolerance in NOD.SCID recipients of both activated diabetogenic CD4+ BDC2...
December 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29249395/synergy-of-immune-checkpoint-blockade-with-a-novel-synthetic-consensus-dna-vaccine-targeting-tert
#15
Elizabeth K Duperret, Megan C Wise, Aspen Trautz, Daniel O Villarreal, Bernadette Ferraro, Jewell Walters, Jian Yan, Amir Khan, Emma Masteller, Laurent Humeau, David B Weiner
Immune checkpoint blockade antibodies are setting a new standard of care for cancer patients. It is therefore important to assess any new immune-based therapies in the context of immune checkpoint blockade. Here, we evaluate the impact of combining a synthetic consensus TERT DNA vaccine that has improved capacity to break tolerance with immune checkpoint inhibitors. We observed that blockade of CTLA-4 or, to a lesser extent, PD-1 synergized with TERT vaccine, generating more robust anti-tumor activity compared to checkpoint alone or vaccine alone...
November 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29248968/contradictory-intrahepatic-immune-responses-activated-in-high-load-hepatitis-c-virus-livers-compared-with-low-load-livers
#16
Mariko Ishibashi, Hiromi Yamaguchi, Yukari Hirotani, Akihisa Sakurada, Toshihide Endo, Masahiko Sugitani, Tadatoshi Takayama, Makoto Makishima, Mariko Esumi
We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area...
December 16, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29248894/a-standardised-frankincense-extract-reduces-disease-activity-in-relapsing-remitting-multiple-sclerosis-the-saba-phase-iia-trial
#17
Klarissa Hanja Stürner, Jan-Patrick Stellmann, Jan Dörr, Friedemann Paul, Tim Friede, Sven Schammler, Stefanie Reinhardt, Susanne Gellissen, Gainet Weissflog, Tobias Djamsched Faizy, Oliver Werz, Sabine Fleischer, Lea A I Vaas, Frank Herrmann, Ole Pless, Roland Martin, Christoph Heesen
OBJECTIVE: To investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). METHODS: We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-to-treatment pilot study with an oral SFE in patients with RRMS (NCT01450124). After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months...
December 16, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29245981/co-targeting-aurora-kinase-with-pd-l1-and-pi3k-abrogates-immune-checkpoint-mediated-proliferation-in-peripheral-t-cell-lymphoma-a-novel-therapeutic-strategy
#18
Shariful Islam, Eric Vick, Bryan Huber, Carla Morales, Catherine Spier, Laurence Cooke, Eric Weterings, Daruka Mahadevan
Peripheral T-cell non-Hodgkin lymphoma (PTCL) are heterogeneous, rare, and aggressive diseases mostly incurable with current cell cycle therapies. Aurora kinases (AKs) are key regulators of mitosis that drive PTCL proliferation. Alisertib (AK inhibitor) has a response rate ∼30% in relapsed and refractory PTCL (SWOG1108). Since PTCL are derived from CD4+/CD8+ cells, we hypothesized that Program Death Ligand-1 (PD-L1) expression is essential for uncontrolled proliferation. Combination of alisertib with PI3Kα (MLN1117) or pan-PI3K inhibition (PF-04691502) or vincristine (VCR) was highly synergistic in PTCL cells...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29239187/-immunotherapy-for-bladder-cancer
#19
T Büchler
Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29238347/langerhans-cells-programmed-by-the-epidermis
#20
REVIEW
Kalum Clayton, Andres F Vallejo, James Davies, Sofia Sirvent, Marta E Polak
Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels. These cells determine the appropriate adaptive immune response (inflammation or tolerance) by interpreting the microenvironmental context in which they encounter foreign substances. In a normal physiological, "non-dangerous" situation, LCs coordinate a continuous state of immune tolerance, preventing unnecessary and harmful immune activation. Conversely, when they sense a danger signal, for example during infection or when the physical integrity of skin has been compromised as a result of a trauma, they instruct T lymphocytes of the adaptive immune system to mount efficient effector responses...
2017: Frontiers in Immunology
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