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https://www.readbyqxmd.com/read/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#1
M Favreau, E Menu, D Gaublomme, K Vanderkerken, S Faict, K Maes, E De Bruyne, S Govindarajan, M Drennan, S Van Calenbergh, X Leleu, L Zabeau, J Tavernier, K Venken, D Elewaut
A hallmark of bone marrow changes with aging is the increase in adipocyte composition, but how this impacts development of multiple myeloma (MM) is unknown. Here, we report the role of the adipokine leptin as master regulator of anti-myeloma tumor immunity by modulating the invariant natural killer T (iNKT) cell function. A marked increase in serum leptin levels and leptin receptor (LR) expression on iNKT cells in MM patients and the 5T33 murine MM model was observed. MM cells and leptin synergistically counteracted anti-tumor functionality of both murine and human iNKT cells...
May 11, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28436457/fasciola-hepatica-glycoconjugates-immuneregulate-dendritic-cells-through-the-dendritic-cell-specific-intercellular-adhesion-molecule-3-grabbing-non-integrin-inducing-t-cell-anergy
#2
Ernesto Rodríguez, Hakan Kalay, Verónica Noya, Natalie Brossard, Cecilia Giacomini, Yvette van Kooyk, Juan J García-Vallejo, Teresa Freire
Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429719/transiently-antigen-primed-b-cells-return-to-naive-like-state-in-absence-of-t-cell-help
#3
Jackson S Turner, Matangi Marthi, Zachary L Benet, Irina Grigorova
The perspective that naive B-cell recognition of antigen in the absence of T-cell help causes cell death or anergy is supported by in vivo studies of B cells that are continuously exposed to self-antigens. However, intravital imaging suggests that early B-cell recognition of large foreign antigens may be transient. Whether B cells are tolerized or can be recruited into humoural immune responses following such encounters is not clear. Here we show that in the presence of T-cell help, single transient antigen acquisition is sufficient to recruit B cells into the germinal centre and induce memory and plasma cell responses...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#4
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28414296/pd-l1-interacts-with-cd80-to-regulate-graft-versus-leukemia-activity-of-donor-cd8-t-cells
#5
Xiong Ni, Qingxiao Song, Kaniel Cassady, Ruishu Deng, Hua Jin, Mingfeng Zhang, Haidong Dong, Stephen Forman, Paul J Martin, Yuan-Zhong Chen, Jianmin Wang, Defu Zeng
Programmed death ligand-1 (PD-L1) interacts with programmed death-1 (PD-1) and the immunostimulatory molecule CD80 and functions as a checkpoint to regulate immune responses. The interaction of PD-L1 with CD80 alone has been shown to exacerbate the severity of graft-versus-host disease (GVHD), whereas costimulation of CD80 and PD-1 ameliorates GVHD. Here we have demonstrated that temporary depletion of donor CD4+ T cells early after hematopoietic cell transplantation effectively prevents GVHD while preserving strong graft-versus-leukemia (GVL) effects in allogeneic and xenogeneic murine GVHD models...
May 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#6
REVIEW
Lydia Dyck, Kingston H G Mills
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells, and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen-presenting cells (APCs) and tumors sends a negative signal to T cells, which can lead to T-cell exhaustion...
May 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28367469/evaluation-of-regulatory-t-cells-in-patients-with-acute-and-chronic-brucellosis
#7
Ali Ganji, Ghasem Mosayebi, Ehsanollah Ghaznavi-Rad, Khadije Khosravi, Nader Zarinfar
BACKGROUND: Brucellosis is one of the most common chronic diseases, with widespread distribution. In spite of cell-mediated immunity (CMI) modulated mainly via activated T-helper type 1 (Th1) cells, brucellosis can advance to chronic disease in about 10-30% of cases. Regulatory T cells (Treg cells) are involved the immune response to brucellosis; however, their role, particularly in the change from the acute to the chronic phase, have not yet been elucidated. The main hypothesis of this study was that Treg cells play critical roles in the progression of brucellosis from the acute to the chronic phase...
April 2017: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28335781/tailored-design-of-nkt-stimulatory-glycolipids-for-polarization-of-immune-responses
#8
REVIEW
Jung-Tung Hung, Jing-Rong Huang, Alice L Yu
Natural killer T (NKT) cell is a distinct population of T lymphocytes that can rapidly release massive amount of Th1 and Th2 cytokines upon the engagement of their T cell receptor with glycolipids presented by CD1d. The secreted cytokines can promote cell-mediated immunity to kill tumor cells and intracellular pathogens, or suppress autoreactive immune cells in autoimmune diseases. Thus, NKT cell is an attractive target for developing new therapeutics to manipulate immune system. The best-known glycolipid to activate NKT cells is α-galactosylceramide (α-GalCer), which has been used as a prototype for designing new NKT stimulatory glycolipids...
March 23, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#9
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28320913/relationship-between-cd4-regulatory-t-cells-and-anergy-in-vivo
#10
REVIEW
Lokesh A Kalekar, Daniel L Mueller
Selective suppression of effector CD4(+) T cell functions is necessary to prevent immune cell-mediated damage to healthy tissues. This appears especially true during pregnancy or in individuals predisposed to autoimmunity. Foxp3(+) regulatory T (Treg) cells and induction of anergy, an acquired state of T cell functional unresponsiveness in Foxp3(-) cells, have both been implicated as mechanisms to suppress dangerous immune responses to tissue-restricted self-Ags. Anergic CD4(+) T cells and Treg cells share a number of phenotypic and mechanistic traits-including the expression of CD73 and folate receptor 4, and the epigenetic modification of Treg cell signature genes-and an interesting relationship between these two subsets has recently emerged...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28267587/cancer-acidity-an-ultimate-frontier-of-tumor-immune-escape-and-a-novel-target-of-immunomodulation
#11
REVIEW
Veronica Huber, Chiara Camisaschi, Angela Berzi, Simona Ferro, Luana Lugini, Tiziana Triulzi, Alessandra Tuccitto, Elda Tagliabue, Chiara Castelli, Licia Rivoltini
The link between cancer metabolism and immunosuppression, inflammation and immune escape has generated major interest in investigating the effects of low pH on tumor immunity. Indeed, microenvironmental acidity may differentially impact on diverse components of tumor immune surveillance, eventually contributing to immune escape and cancer progression. Although the molecular pathways underlying acidity-related immune dysfunctions are just emerging, initial evidence indicates that antitumor effectors such as T and NK cells tend to lose their function and undergo a state of mostly reversible anergy followed by apoptosis, when exposed to low pH environment...
March 6, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28260519/immune-tolerance-of-mesenchymal-stem-cells-and-induction-of-skin-allograft-tolerance
#12
Tengxiao Ma, Xiao Wang, Duyin Jiang
Mesenchymal stem cells not only possess reparative properties, but also have immunomodulatory effect. Owing to the properties, they have been proposed to be hopeful candidates for cell therapy in the process of organ transplantation. In the preclinical researches, it shows that MSCs is capable of prolonging graft survival and inducing tolerance in some cases. Various mechanisms of immune tolerance were reported before, such as tolerogenic dendritic cells, induction of apoptosis, regulatory T cells, mixed chimerism, soluble factors and anergy...
March 1, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28228105/mesenchymal-stromal-cells-as-vehicles-of-tetravalent-bispecific-tandab-cd3-cd19-for-the-treatment-of-b-cell-lymphoma-combined-with-ido-pathway-inhibitor-d-1-methyl-tryptophan
#13
Xiaolong Zhang, Yuanyuan Yang, Leisheng Zhang, Yang Lu, Qing Zhang, Dongmei Fan, Yizhi Zhang, Yanjun Zhang, Zhou Ye, Dongsheng Xiong
BACKGROUND: Although blinatumomab, a bispecific T cell engaging antibody, exhibits high clinical response rates in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL), it still has some limitations because of its short half-life. Mesenchymal stromal cells (MSCs) represent an attractive approach for delivery of therapeutic agents to cancer sites owing to their tropism towards tumors, but their immunosuppression capabilities, especially induced by indoleamine 2,3-dioxygenase (IDO), should also be taken into consideration...
February 23, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28215626/dendritic-cells-that-highly-express-socs1-induce-t-cell-hypo-responsiveness-and-prolong-islet-allograft-survival
#14
Xinjun Lu, Maogen Chen, Zhicheng Xue, Xuzhi Zhang, Jiejie Xu, Linwei Wu, Ronghai Deng, Yi Ma
The capability of dendritic cells (DCs) to induce an immune response or immune tolerance is dependent on their status. Suppressor of cytokine signaling 1 (SOCS1) is a pivotal regulator that participates in negative feedback of the JAK-STAT pathway, which plays a key role in the differentiation, activation, and maturation of DCs. DCs that highly express SOCS1 may modulate DCs, and induce immune anergy or immune tolerance. In this study, we transduced DCs with the recombinant adenovirus Ad5F35 to highly express SOCS1...
February 2, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28212788/immunology-of-alveolar-and%C3%A2-cystic-echinococcosis-ae-and-ce
#15
B Gottstein, P Soboslay, E Ortona, J Wang, A Siracusano, D Α Vuitton
Cystic and alveolar echinococcosis are severe chronic helminthic diseases caused by the cystic growth or the intrahepatic tumour-like growth of the metacestode of Echinococcus granulosus or Echinococcus multilocularis, respectively. Both parasites have evolved sophisticated strategies to escape host immune responses, mainly by manipulating and directing this immune response towards anergy and/or tolerance. Recent research studies have revealed a number of respective immunoregulatory mechanisms related to macrophages and dendritic cell as well as T cell activities (regulatory T cells, Tregs)...
2017: Advances in Parasitology
https://www.readbyqxmd.com/read/28208221/increased-fas-ligand-expression-of-peripheral-b-1-cells-correlated-with-cd4-t-cell-apoptosis-in-filarial-infected-patients
#16
R Mishra, S K Panda, P K Sahoo, M S Bal, A K Satapathy
Cellular hyporesponsiveness observed during helminth infections is attributed to factors such as antigen-presenting cells (APC) dysfunction, increased interleukin-10(IL-10), regulatory T cells and induction of CD4(+) T (Th)-cell apoptosis. Increased Fas ligand (FasL) expression on the surface of B-1 cells and induction of apoptosis of Th cells by FasL-expressing B-1 cells due to helminth infection were demonstrated in murine model of helminth infection where as profile of FasL expression, Th-cell apoptosis and correlation between these two populations of cells in clinical filariasis remain unknown...
April 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28160999/-the-immune-checkpoints-how-does-it-work
#17
Clémence Granier, Vassili Soumelis, Marion Mandavit, Laure Gibault, Radia Belazzoug, Eléonore de Guillebon, Cécile Badoual, Eric Tartour, Hélène Roussel
Costimulatory molecules allow the full lymphocyte activation, whereas co-inhibitory molecules are negative counterparts that act as immune regulators, avoiding excessive response. In some context of chronic inflammation such as cancer, co-inhibitory immune checkpoint as CTLA-4, PD-1, Lag-3, Tim-3 can accumulate at the membrane of T cells leading to a state of anergy and therefore the loss of tumor growth control. Consequently, these immune checkpoints are considered as potential target in the treatment of cancer...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28122965/mycobacterium-tuberculosis-membrane-vesicles-inhibit-t-cell-activation
#18
Jaffre J Athman, Obondo J Sande, Sarah G Groft, Scott M Reba, Nancy Nagy, Pamela A Wearsch, Edward T Richardson, Roxana Rojas, W Henry Boom, Supriya Shukla, Clifford V Harding
Mycobacterium tuberculosis utilizes multiple mechanisms to evade host immune responses, and inhibition of effector CD4(+) T cell responses by M. tuberculosis may contribute to immune evasion. TCR signaling is inhibited by M. tuberculosis cell envelope lipoglycans, such as lipoarabinomannan and lipomannan, but a mechanism for lipoglycans to traffic from M. tuberculosis within infected macrophages to reach T cells is unknown. In these studies, we found that membrane vesicles produced by M. tuberculosis and released from infected macrophages inhibited the activation of CD4(+) T cells, as indicated by reduced production of IL-2 and reduced T cell proliferation...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28114324/grail-and-otubain-1-are-related-to-t-cell-hyporesponsiveness-during-trypanosoma-cruzi-infection
#19
Cinthia C Stempin, Jorge D Rojas Marquez, Yamile Ana, Fabio M Cerban
BACKGROUND: Trypanosoma cruzi infection is associated with severe T cell unresponsiveness to antigens and mitogens and is characterized by decreased IL-2 synthesis. In addition, the acquisition of the anergic phenotype is correlated with upregulation of "gene related to anergy in lymphocytes" (GRAIL) protein in CD4 T cells. We therefore sought to examine the role of GRAIL in CD4 T cell proliferation during T. cruzi infection. METHODOLOGY/PRINCIPAL FINDINGS: Balb/c mice were infected intraperitoneally with 500 blood-derived trypomastigotes of Tulahuen strain, and spleen cells from control non-infected or infected animals were obtained...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28111042/-immunotherapy-in-uropathology
#20
Virginie Verkarre, Hélène Roussel, Clémence Granier, Eric Tartour, Yves Allory
The algorithms for treatment of metastatic cancers are evolving due to positive results obtained with immunotherapy. Therapeutics approaches to stimulate the immune system have already been used in the treatment of kidney and bladder cancer, such as the administration of cytokines and BCG therapy, confirming the immunogenicity of these tumors. The aim of immunotherapies is not only to activate the immune system against tumor cells, but also to take into account the tumor-induced suppressive microenvironment, in particular by removing the anergy of T-cell lymphocytes, and by targeting the co-stimulation inhibitors molecules...
February 2017: Annales de Pathologie
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