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CD8 tolerance

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https://www.readbyqxmd.com/read/28542586/antigen-delivery-to-dendritic-cells-shapes-human-cd4-and-cd8-t-cell-memory-responses-to-staphylococcus-aureus
#1
Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4+ and CD8+ T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4+ and CD8+ T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542574/combination-therapy-of-cancer-with-cancer-vaccine-and-immune-checkpoint-inhibitors-a-mathematical-model
#2
Xiulan Lai, Avner Friedman
In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at 'roughly' twice the dosage level; if that is the case, then we say that there is a positive 'synergy' for this combination of dosages...
2017: PloS One
https://www.readbyqxmd.com/read/28536029/specific-humoral-and-cellular-immune-responses-in-cancer-patients-undergoing-chronic-immunization-with-a-vegf-based-therapeutic-vaccine
#3
Yanelys Morera, Javier Sánchez, Mónica Bequet-Romero, Katty-Hind Selman-Housein, Ana de la Torre, Francisco Hernández-Bernal, Yenima Martín, Acralys Garabito, Jesús Piñero, Cimara Bermúdez, Josué de la Torre, Marta Ayala, Jorge V Gavilondo
CIGB-247 is a cancer therapeutic vaccine, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the adjuvant VSSP, a bacterially-derived adjuvant. The vaccine have demonstrated efficacy in several murine malignancy models. These studies supported the rationale for a phase I clinical trial where safety, tolerance, and immunogenicity of CIGB-247 was studied in patients with advanced solid tumors at three antigen dose level. Surviving individuals of this clinical trial were eligible to receive off-trial voluntary re-immunizations...
May 20, 2017: Vaccine
https://www.readbyqxmd.com/read/28529646/peptide-vaccination-in-the-presence-of-adjuvants-in-patients-after-hematopoietic-stem-cell-transplantation-with-cd4-t-cell-reconstitution-elicits-consistent-cd8-t-cell-responses
#4
Michael Schmitt, Anita Schmitt, Markus Wiesneth, Angela Hückelhoven, Zeguang Wu, Jürgen Kuball, Lei Wang, Peter Schauwecker, Susanne Hofmann, Marlies Götz, Birgit Michels, Birgit Maccari, Patrick Wuchter, Volker Eckstein, Thomas Mertens, Paul Schnitzler, Hartmut Döhner, Anthony D Ho, Donald W Bunjes, Peter Dreger, Hubert Schrezenmeier, Jochen Greiner
Rationale: Patients receiving an allogeneic stem cell graft from cytomegalovirus (CMV) seronegative donors are particularly prone to CMV reactivation with a high risk of disease and mortality. Therefore we developed and manufactured a novel vaccine and initiated a clinical phase I trial with a CMV phosphoprotein 65 (CMVpp65)-derived peptide. Methods: Ten patients after allogeneic stem cell transplantation received four vaccinations at a biweekly interval. All patients were monitored for CMVpp65 antigenemia...
2017: Theranostics
https://www.readbyqxmd.com/read/28529323/an-immunogenic-phenotype-in-paternal-antigen-specific-cd8-t-cells-at-embryo-implantation-elicits-later-fetal-loss-in-mice
#5
Lachlan M Moldenhauer, Kerrilyn R Diener, John D Hayball, Sarah A Robertson
Central to pregnancy success is a state of T cell tolerance to paternal antigens, which is initiated at conception. The role and regulation of specific phenotypes of CD8(+) T cells in mediating pregnancy tolerance is not clear. This study aimed to investigate the impact on pregnancy outcome of altering the cytokine environment during maternal CD8(+) T cell priming in early pregnancy. Transgenic Act-mOVA male mice were mated to C57BL/6 (B6) females to generate fetuses expressing ovalbumin (OVA) as a model paternal antigen...
May 22, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28521429/b-cells-inhibit-the-antitumor-immunity-against-an-established-murine-fibrosarcoma
#6
Andrea Maglioco, Damián G Machuca, María Noel Badano, Paula Nannini, Gabriela V Camerano, Héctor Costa, Roberto Meiss, Raúl A Ruggiero, Mirta Giordano, Graciela I Dran
Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B(+)IL-10(+) cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B(+)IL-10(+) cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28508475/functional-properties-of-peripheral-cd8-%C3%A2-t-cells-in-patients-with-repeated-implantation-failure
#7
Biao Yin, Yong Zeng, Tonghua Wu, Shuyi Yu, Jian Xu, Su Liu, Lianghui Diao, Zhenfu Zhao, Desheng Liang, Yuye Li
CD8(+) T cells are the main candidates to recognize and respond to fetal HLA-C at the fetal-maternal interface, but data on the amount of peripheral CD8(+) T cells and their functions during the window of implantation in recurrent implantation failure (RIF) patients are limited. Peripheral blood was obtained from 56 women with RIF and 16 fertile women in the mid-luteal phase of the menstrual cycle, and the CD8(+) T cells were determined by FACS analysis. No statistical differences in the proportion of peripheral CD8(+) T cells were observed among the women with RIF and the control group...
May 15, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28498840/a-third-generation-vaccine-for-human-visceral-leishmaniasis-and-post-kala-azar-dermal-leishmaniasis-first-in-human-trial-of-chad63-kh
#8
Mohamed Osman, Anoop Mistry, Ada Keding, Rhian Gabe, Elizabeth Cook, Sarah Forrester, Rebecca Wiggins, Stefania Di Marco, Stefano Colloca, Loredana Siani, Riccardo Cortese, Deborah F Smith, Toni Aebischer, Paul M Kaye, Charles J Lacey
BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs...
May 12, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28494555/-liver-sinusoidal-endothelial-cells-regulate-adaptive-immune-tolerance-in-the-liver
#9
Y Q Du, C Sun, S M Huang, D L Yang, J Wu
Liver sinusoidal endothelial cells are a major group of nonparenchymal cells in the liver and are involved in immunological surveillance of the liver through the expression of various scavenger receptors and pattern recognition receptors. However, in case of several physiological states, viral infections, and tumor environment, liver sinusoidal endothelial cells maintain immune tolerance in the liver through various mechanisms and cause persistent viral infection and tumor metastasis. This article reviews the mechanisms of immune tolerance of CD4 + T cells and CD8 + T cells in the liver induced by liver sinusoidal endothelial cells...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28491873/b-cd8-t-cell-interactions-in-the-anti-idiotypic-response-against-a-self-antibody
#10
Darel Martínez, Amaury Pupo, Lianet Cabrera, Judith Raymond, Nichol E Holodick, Ana María Hernández
P3 is a murine, germline, IgM mAb that recognizes N-glycolylated gangliosides and other self-antigens. This antibody is able to induce an anti-idiotypic IgG response and B-T idiotypic cascade, even in the absence of any adjuvant or carrier protein. P3 mAb immunization induces the expression of activation markers in a significant percentage of B-1a cells in vivo. Interestingly, transfer of both B-1a and B-2 to BALB/Xid mice was required to recover anti-P3 IgG response in this model. In fact, P3 mAb activated B-2 cells, in vitro, inducing secretion of IFN-γ and IL-4, although this activation was not detected ex vivo...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28484450/il-2-mediated-in-vivo-expansion-of-regulatory-t-cells-combined-with-cd154-cd40-co-stimulation-blockade-but-not-ctla-4-ig-prolongs-allograft-survival-in-naive-and-sensitized-mice
#11
Lerisa Govender, Jean-Christophe Wyss, Rajesh Kumar, Manuel Pascual, Dela Golshayan
In recent years, regulatory T cells (Treg)-based immunotherapy has emerged as a promising strategy to promote operational tolerance after solid organ transplantation (SOT). However, a main hurdle for the therapeutic use of Treg in transplantation is their low frequency, particularly in non-lymphopenic hosts. We aimed to expand Treg directly in vivo and determine their efficacy in promoting donor-specific tolerance, using a stringent experimental model. Administration of the IL-2/JES6-1 immune complex at the time of transplantation resulted in significant expansion of donor-specific Treg, which suppressed alloreactive T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28483787/a-sting-agonist-given-with-ox40-receptor-and-pd-l1-modulators-primes-immunity-and-reduces-tumor-growth-in-tolerized-mice
#12
Jeremy B Foote, Marleen Kok, James M Leatherman, Todd D Armstrong, Bridget C Marcinkowski, Laureen S Ojalvo, David B Kanne, Elizabeth M Jaffee, Thomas W Dubensky, Leisha A Emens
STING signaling induces interferon-β (IFNβ) production by intratumoral dendritic cells (DCs), driving T-cell priming and recruitment into the tumor microenvironment (TME). We examined to what extent pre-existing antigen tolerance influenced the efficacy of in situ delivery of a potent STING-activating cyclic dinucleotide (CDN), ADU S-100, against established HER-2(+) breast tumors. ADU S-100 induced HER-2-specific CD8(+) T-cell priming and durable tumor clearance in 100% of nontolerant parental FVB/N mice...
May 8, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28482051/biomarkers-of-chronic-acrolein-inhalation-exposure-in-mice-implications-for-tobacco-product-induced-toxicity
#13
Daniel J Conklin, Marina V Malovichko, Iris Zeller, Trinath P Das, Tatiana V Krivokhizhina, Blake H Lynch, Pawel Lorkiewicz, Abhinav Agarwal, Nalinie Wickramasinghe, Petra Haberzettl, Srinivas D Sithu, Jasmit Shah, Timothy E O'Toole, Shesh N Rai, Aruni Bhatnagar, Sanjay Srivastava
Exposure to tobacco smoke, which contains several harmful and potentially harmful constituents such as acrolein increases cardiovascular disease (CVD) risk. Although high acrolein levels induce pervasive cardiovascular injury, the effects of low-level exposure remain unknown and sensitive biomarkers of acrolein toxicity have not been identified. Identification of such biomarkers is essential to assess the toxicity of acrolein present at low levels in the ambient air or in new tobacco products such as e-cigarettes...
May 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28475554/sustained-viral-suppression-in-hiv-infected-children-on-once-daily-lopinavir-ritonavir-in-clinical-practice
#14
Ivar P E Gondrie, Diane E T Bastiaans, Pieter L A Fraaij, Gertjan J A Driessen, Linda C Van Der Knaap, Eline G Visser, Petronette Van Jaarsveld, Ronald de Groot, Nico G Hartwig, David M Burger, Annemarie M C Van Rossum
BACKGROUND: The use of lopinavir/ritonavir once-daily (LPV/r QD) has not been approved for children. Good short-term clinical, virological and immunological outcomes have been observed in children on LPV/r QD. METHODS: We evaluated the long-term effectiveness of a LPV/r QD containing regimen in HIV-1 infected children in clinical practice. Selected children (aged 0-18 years) with an undetectable HIV-1 RNA viral load (<50 copies/mL) for at least 6 months on a twice-daily (BID) LPV/r-containing regimen switched to LPV/r QD...
May 4, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28473406/phase-i-multicenter-trial-of-brentuximab-vedotin-for-steroid-refractory-acute-graft-vs-host-disease-gvhd
#15
Yi-Bin Chen, Miguel-Angel Perales, Shuli Li, Maria Kempner, Carol Reynolds, Jami Brown, Yvonne A Efebera, Steven M Devine, Areej El-Jawahri, Steven L McAfee, Thomas R Spitzer, Robert J Soiffer, Jerome Ritz, Corey Cutler
Therapy for steroid-refractory acute GVHD remains suboptimal. Pre-clinical data demonstrate increased CD30 expression on activated CD8(+) T-cells during acute GVHD. Brentuximab vedotin (BV) is an antibody-drug conjugate targeting CD30. We conducted a multicenter phase I trial (ClinicalTrials.gov NCT01940796) in 34 patients to establish the maximum tolerated dose (MTD) of BV for treatment of steroid-refractory acute GVHD. A 3+3 cohort design was conducted initially with BV given weekly x 3 doses followed by maintenance dosing (initial dose 0...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28469254/immune-checkpoint-protein-vista-critically-regulates-the-il-23-il-17-inflammatory-axis
#16
Na Li, Wenwen Xu, Ying Yuan, Natarajan Ayithan, Yasutomo Imai, Xuesong Wu, Halli Miller, Michael Olson, Yunfeng Feng, Yina H Huang, Mary Jo Turk, Samuel T Hwang, Subramaniam Malarkannan, Li Wang
V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an inhibitory immune-checkpoint molecule that suppresses CD4(+) and CD8(+) T cell activation when expressed on antigen-presenting cells. Vsir (-/-) mice developed loss of peripheral tolerance and multi-organ chronic inflammatory phenotypes. Vsir (-/-) CD4(+) and CD8(+) T cells were hyper-responsive towards self- and foreign antigens. Whether or not VISTA regulates innate immunity is unknown. Using a murine model of psoriasis induced by TLR7 agonist imiquimod (IMQ), we show that VISTA deficiency exacerbated psoriasiform inflammation...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28469082/ctla4-ig-in-combination-with-fty720-promotes-allograft-survival-in-sensitized-recipients
#17
Stella H Khiew, Jinghui Yang, James S Young, Jianjun Chen, Qiang Wang, Dengping Yin, Vinh Vu, Michelle L Miller, Roger Sciammas, Maria-Luisa Alegre, Anita S Chong
Despite recent evidence of improved graft outcomes and safety, the high incidence of early acute cellular rejection with belatacept, a high-affinity CTLA4-Ig, has limited its use in clinical transplantation. Here we define how the incomplete control of endogenous donor-reactive memory T cells results in belatacept-resistant rejection in an experimental model of BALB/c.2W-OVA donor heart transplantation into C57BL/6 recipients presensitized to donor splenocytes. These sensitized mice harbored modestly elevated numbers of endogenous donor-specific memory T cells and alloantibodies compared with naive recipients...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28466476/numerical-and-functional-defects-in-cd8-cd28-t-suppressor-lymphocytes-from-patients-with-primary-immune-thrombocytopenia
#18
Huiyuan Li, Yating Hao, Donglei Zhang, Wenjie Liu, Yang Li, Mingen Lyu, Rongfeng Fu, Feng Xue, Xiaofan Liu, Renchi Yang
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder, and loss of immune tolerance has been implicated in ITP pathogenesis. CD8(+) CD28(-) suppressor (Ts) cells have an immunosuppression function and are involved in several autoimmune disorders. However, the role of Ts cells in ITP is currently not clear. Here, flow cytometry was used to detect the CD8(+) CD28(-) CD127(-) proportion, which was decreased in active ITP patients compared with that of controls. Function analysis showed that immunosuppression of CD8(+) CD28(-) Ts cells in ITP patients was impaired...
May 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28455654/metabolically-inactive-insulin-analogue-does-not-prevent-autoimmune-diabetes-in-nod-mice
#19
Juha Grönholm, Philippe P Pagni, Minh N Pham, Claire B Gibson, Paul F Macomber, José Luis Vela, Matthias von Herrath, Michael J Lenardo
AIMS/HYPOTHESIS: Insulin is widely considered to be a driver antigen in type 1 diabetes in humans and in mouse models of the disease. Therefore, insulin or insulin analogues are candidates for tolerogenic drugs to prevent disease onset in individuals with risk of diabetes. Previous experiments have shown that autoimmune diabetes can be prevented in NOD mice by repeated doses of insulin administered via an oral, nasal or parenteral route, but clinical trials in humans have not succeeded...
April 28, 2017: Diabetologia
https://www.readbyqxmd.com/read/28442553/nlrp3-signaling-drives-macrophage-induced-adaptive-immune-suppression-in-pancreatic-carcinoma
#20
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Gautam S D Balasubramania Pandian, Shivraj Savadkar, Ki Buom Lee, Alejandro Torres-Hernandez, Berk Aykut, Brian Diskin, Wei Wang, Mohammad S Farooq, Arif I Mahmud, Gregor Werba, Eduardo J Morales, Sarah Lall, Benjamin J Wadowski, Amanda G Rubin, Matthew E Berman, Rajkishen Narayanan, Mautin Hundeyin, George Miller
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4(+) T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8(+) T cell activation...
April 25, 2017: Journal of Experimental Medicine
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