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https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#1
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#2
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21(low) phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28500564/calcium-signaling-from-normal-b-cell-development-to-tolerance-breakdown-and-autoimmunity
#3
REVIEW
Patrice Hemon, Yves Renaudineau, Marjolaine Debant, Nelig Le Goux, Sreya Mukherjee, Wesley Brooks, Olivier Mignen
Maintenance of self-tolerance of auto-reactive lymphocytes is a fundamental mechanism to prevent the onset of autoimmune diseases. Deciphering the mechanisms involved in the deregulations leading to tolerance disruption and autoimmunity is still a major area of interest to identify new therapeutic targets and options. Ca(2+) signaling plays a major role in B cell normal development and is therefore finely tuned by B cell receptor (BCR)-dependent and independent pathways. Developmental changes in the characteristics of BCR-dependent Ca(2+) signals as well as the modulation of basal intracellular concentration ([Ca(2+)]i) contribute strongly to self-tolerance maintaining mechanisms responsible for the physical or functional elimination of autoreactive B cells such as clonal deletion, receptor editing, and anergy...
May 13, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28490813/leptin-receptor-antagonism-of-inkt-cell-function-a-novel-strategy-to-combat-multiple-myeloma
#4
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/28479213/original-antigenic-sin-a-comprehensive-review
#5
REVIEW
Anup Vatti, Diana M Monsalve, Yovana Pacheco, Christopher Chang, Juan-Manuel Anaya, M Eric Gershwin
The concept of "original antigenic sin" was first proposed by Thomas Francis, Jr. in 1960. This phenomenon has the potential to rewrite what we understand about how the immune system responds to infections and its mechanistic implications on how vaccines should be designed. Antigenic sin has been demonstrated to occur in several infectious diseases in both animals and humans, including human influenza infection and dengue fever. The basis of "original antigenic sin" requires immunological memory, and our immune system ability to autocorrect...
May 5, 2017: Journal of Autoimmunity
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
#6
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
#7
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
#8
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
#9
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/28411047/immunodepression-after-cpb-cytokine-dynamics-and-clinics-after-pediatric-cardiac-surgery-a-prospective-trial
#10
Georgia Justus, Christoph Walker, Lisa-Maria Rosenthal, Felix Berger, Oliver Miera, Katharina Rose Luise Schmitt
BACKGROUND: Corrective surgery for congenital heart defects is known to trigger a severe immune reaction. There has been extensive research on the effects of inflammation after cardiopulmonary bypass (CPB). Interestingly, monocytes are observed to be non-responsive to stimulation with lipopolysaccharide (LPS) under these conditions, indicating a state of immunodepression, which lays the ground for second hit infections after cardiosurgery with CPB. OBJECTIVES: The aim of this prospective study was to analyze immunodepression after pediatric cardiopulmonary bypass and to differentiate the effects of monocytic anergy on postoperative outcome...
April 11, 2017: Cytokine
https://www.readbyqxmd.com/read/28408984/b-cell-tolerance-and-autoimmunity
#11
REVIEW
Takeshi Tsubata
Self-reactive B cells are tolerized at various stages of B-cell development and differentiation, including the immature B-cell stage (central tolerance) and the germinal center (GC) B-cell stage, and B-cell tolerance involves various mechanisms such as deletion, anergy, and receptor editing. Self-reactive B cells generated by random immunoglobulin variable gene rearrangements are tolerized by central tolerance and anergy in the periphery, and these processes involve apoptosis regulated by Bim, a pro-apoptotic member of the Bcl-2 family, and regulation of B-cell signaling by various phosphatases, including SHIP-1 and SHP-1...
2017: F1000Research
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#12
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
#13
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
#14
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
#15
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
#16
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/28303767/immunomonitoring-reveals-interruption-of-anergy-after-vaccination-in-a-case-of-type-2-papillary-renal-cell-carcinoma
#17
Maria A Clavijo-Salomon, Patricia C Bergami-Santos, José Alexandre M Barbuto
With the enormous and growing interest in the clinical application of immunotherapy, we are currently facing the need to accurately monitor the immune function of cancer patients. Here, we describe changes in the immune status of a patient with metastatic type-2-papillary renal cell carcinoma, before and after surgery and subsequent immunotherapy with a dendritic cell-tumor cell hybrid vaccine. Through the accurate assessment of monocyte-derived dendritic cells (Mo-DCs) function, we show that Mo-DCs were freed from tumor-induced maturation blockage by tumor resection surgery, while Mo-DCs-tumor induced suppression and anergy were only interrupted by the vaccination treatment...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28267587/cancer-acidity-an-ultimate-frontier-of-tumor-immune-escape-and-a-novel-target-of-immunomodulation
#18
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...
April 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28260519/immune-tolerance-of-mesenchymal-stem-cells-and-induction-of-skin-allograft-tolerance
#19
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
#20
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
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