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https://www.readbyqxmd.com/read/28521278/scaffold-protein-jlp-mediates-tcr-initiated-cd4-t-cell-activation-and-cd154-expression
#1
Qi Yan, Cheng Yang, Qiang Fu, Zhaowei Chen, Shan Liu, Dou Fu, Rahmat N Rahman, Ryota Nakazato, Katsuji Yoshioka, Sam K P Kung, Guohua Ding, Huiming Wang
CD4(+) T-cell activation and its subsequent induction of CD154 (CD40 ligand, CD40L) expression are pivotal in shaping both the humoral and cellular immune responses. Scaffold protein JLP regulates signal transduction pathways and molecular trafficking inside cells, thus represents a critical component in maintaining cellular functions. Its role in regulating CD4(+) T-cell activation and CD154 expression, however, is unclear. Here, we demonstrated expression of JLP in mouse tissues of lymph nodes, thymus, spleen, and also CD4(+) T cells...
May 15, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28503733/long-term-safety-from-transmission-of-porcine-endogenous-retrovirus-after-pig-to-non-human-primate-corneal-transplantation
#2
Hyuk Jin Choi, Jiyeon Kim, Jae Young Kim, Hyun Ju Lee, Won Ryang Wee, Mee Kum Kim, Eung Soo Hwang
BACKGROUND: The risk of xenozoonosis mainly by porcine endogenous retrovirus (PERV) has been considered as one of the main hurdles in xenotransplantation and therefore should be elucidated prior to the clinical use of porcine corneal grafts. Accordingly, an investigation was performed to analyze the infectivity of PERVs from porcine keratocytes to human cells, and the long-term risk of transmission of PERVs was determined using pig-to-non-human primate (NHP) corneal transplantation models...
May 14, 2017: Xenotransplantation
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
#3
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/28484052/chronic-critical-illness-from-sepsis-is-associated-with-an-enhanced-tcr-response
#4
Farina Borken, Robby Markwart, Robert P Requardt, Katja Schubert, Michal Spacek, Miroslav Verner, Stefan Rückriem, André Scherag, Frank Oehmichen, Frank M Brunkhorst, Ignacio Rubio
Sepsis is characterized by a disproportionate host response to infection that often culminates in multiple organ failure. Current concepts invoke a deregulated immune reaction involving features of hyperinflammation, as well as protracted immune suppression. However, owing to the scarcity of human data, the precise origin of a long-term suppression of adaptive immunity remains doubtful. We report on an explorative clinical study of chronic critical illness (CCI) patients aimed at assessing the long-term consequences of sepsis on T cell function...
May 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28469980/znt7-binds-to-cd40-and-influences-cd154-triggered-p38-mapk-activity-in-b-lymphocytes-a-possible-regulatory-mechanism-for-zinc-in-immune-function
#5
Surapun Tepaamorndech, Pieter Oort, Catherine P Kirschke, Yimeng Cai, Liping Huang
Zinc deficiency impairs the immune system leading to frequent infections. Although zinc is known to play critical roles in maintaining healthy immune function, the underlying molecular targets are largely unknown. In this study, we demonstrate that zinc is important for the CD154-CD40-mediated activation of downstream signaling pathways in human B lymphocytes. CD40 is a receptor localized on the cell surface of many immune cells, including B lymphocytes. It binds to CD154, a membrane protein expressed on antigen-activated T helper (Th) lymphocytes...
May 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28417501/d-dimer-level-in-association-with-humoral-responses-negatively-correlates-with-survival-of-porcine-islet-grafts-in-non-human-primates-with-immunosuppression
#6
Hee Jung Kang, Haneulnari Lee, Eun Mi Park, Jong-Min Kim, Byoung-Hoon Min, Chung-Gyu Park
BACKGROUND: Several immunosuppression (IS) regimens achieve long-term graft survival in non-human primates (NHPs) after porcine islet transplantation (PITx), but their success rates vary. To understand the mechanism of graft loss, we investigated the relationships between graft survival and humoral or inflammatory responses for maintenance IS in NHPs after PITx. METHODS: Islets purified from adult wild-type pigs were intraportally transplanted into streptozotocin-induced diabetic rhesus monkeys...
April 18, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28413134/the-in-vitro-mimic%C3%A2-platform-reflects-age-associated-changes-in-immunological-responses-after-influenza-vaccination
#7
Allison Dauner, Pankaj Agrawal, Jose Salvatico, Tenekua Tapia, Vipra Dhir, S Farzana Shaik, Donald R Drake, Anthony M Byers
Increasing research and development costs coupled with growing concerns over healthcare expenditures necessitate the generation of pre-clinical testing models better able to predict the efficacy of vaccines, drugs and biologics. An ideal system for evaluating vaccine immunogenicity will not only be reliable but also physiologically relevant, able to be influenced by immunomodulatory characteristics such as age or previous exposure to pathogens. We have previously described a fully autologous human cell-based MIMIC® (Modular IMmune In vitro Construct) platform which enables the evaluation of innate and adaptive immunity in vitro, including naïve and recall responses...
April 13, 2017: Vaccine
https://www.readbyqxmd.com/read/28393447/anti-cd40-antibody-mediated-costimulation-blockade-promotes-long-term-survival-of-deep-lamellar-porcine-corneal-grafts-in-non-human-primates
#8
Jaeyoung Kim, Dong Hyun Kim, Hyuk Jin Choi, Hyun Ju Lee, Hee Jung Kang, Chung-Gyu Park, Eung-Soo Hwang, Mee Kum Kim, Won Ryang Wee
BACKGROUND: Corneal xenotransplantation is an effective solution for the shortage of human donor corneas, and the porcine cornea may be a suitable candidate for the donor cornea because of its optical similarity with humans. However, it is necessary to administer additional immunosuppressants to overcome antigenic differences. We aimed to investigate the feasibility of porcine corneas with anti-CD40 antibody-mediated costimulation blockade in a clinically applicable pig-to-non-human primate corneal xenotransplantation model...
April 10, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28304254/clinical-trypanosoma-cruzi-disease-after-cardiac-transplantation-in-a-cynomolgus-macaque-macaca-fascicularis
#9
Elana R Rybak, Steve Shipley, Ivan Tatarov, Tianshu Zhang, Wenji Sun, Gheorghe Braileanu, Lars Burdorf, Evelyn Sievert, Agnes M Azimzadeh, Louis J DeTolla, Richard N Pierson Iii
A cynomolgus macaque received a heterotopic cardiac allograft as part of a transplant study, with monoclonal antibodies targeted to specific immune costimulation molecules (CD154, CD28) but no traditional immunosuppressive therapy after surgery. Clinical anemia was detected on postoperative day (POD) 35 and had worsened (Hgb, 2.3 g/dL; Hct = 7.3%) by POD 47, despite type-matched whole-blood transfusions. After a total of 4 blood transfusions, hematologic parameters were improved (Hgb, 5.9 g/dL; Hct, 18.7%)...
December 1, 2016: Comparative Medicine
https://www.readbyqxmd.com/read/28192476/th40-cells-cd4-cd40-tcells-drive-a-more-severe-form-of-experimental-autoimmune-encephalomyelitis-than-conventional-cd4-t-cells
#10
Gisela M Vaitaitis, Martin G Yussman, Dan M Waid, David H Wagner
CD40-CD154 interaction is critically involved in autoimmune diseases, and CD4 T cells play a dominant role in the Experimental Autoimmune Encephalomyelitis (EAE) model of Multiple Sclerosis (MS). CD4 T cells expressing CD40 (Th40) are pathogenic in type I diabetes but have not been evaluated in EAE. We demonstrate here that Th40 cells drive a rapid, more severe EAE disease course than conventional CD4 T cells. Adoptively transferred Th40 cells are present in lesions in the CNS and are associated with wide spread demyelination...
2017: PloS One
https://www.readbyqxmd.com/read/28192147/systemic-innate-immune-activation-in-food-protein-induced-enterocolitis-syndrome
#11
Ritobrata Goswami, Ana Belen Blazquez, Roman Kosoy, Adeeb Rahman, Anna Nowak-Węgrzyn, M Cecilia Berin
BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated food allergy of infancy whose pathophysiology is poorly understood. OBJECTIVES: We set out to identify and phenotype allergen-responsive cells in peripheral blood of a cohort of subjects undergoing supervised food challenge for FPIES. METHODS: We profiled antigen-responsive cells in PBMCs by flow cytometry, and examined cells in whole blood obtained before and after challenge by CyTOF mass cytometry and RNAseq...
February 10, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28149882/simian-immunodeficiency-virus-confounds-t-follicular-helper-t-cells-and-the-germinal-centre
#12
COMMENT
Tom N Lea-Henry, Simon H Jiang
Yamamoto et al. have studied T follicular helper (TFH) and germinal centre (GC) responses after infection of rhesus macaques (RM) infected with simian immunodeficiency virus (SIV). In this study the authors examined the behaviour of TFH, reproducing infection-associated TFH accumulation and their association with the quality of antibody responses against cross-clade viral epitopes. The authors correlate TFHIL4 and CD154 expression with superior antibody responses. Accumulation of TFH was accompanied by aberrant expression of non-TFH transcriptional regulators such as BLIMP1 in TFH, suggesting viral induced abnormalities may affect TFH function...
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28141921/a-tale-of-two-pathways-renewing-the-promise-of-anti-cd40l-blockade
#13
EDITORIAL
A W Thomson, M B Ezzelarab
No abstract text is available yet for this article.
January 31, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28119073/harnessing-the-immunotherapeutic-potential-of-t-lymphocyte-co-signaling-molecules-in-transplantation
#14
REVIEW
Abdul W Ansari, Mohammad A Khan, Reinhold E Schmidt, Dieter C Broering
Alloantigen-specific T-cell triggered immunopathological events are responsible for rapid allograft rejection. The co-signaling pathways orchestrated by co-stimulatory and co-inhibitory molecules are critical for optimal T-cell effector function. Therefore, selective blockade of pathways that control T-cell immunity may offer an attractive therapeutic strategy to manipulate cell mediated allogenic responses. For example, CD28, CTLA-4 and CD154 receptor blockade have proven beneficial in maintaining T-cell tolerance against transplanted organs in experimental animal models as well as in clinical trials...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/28106273/the-immunoglobulin-superfamily-member-cd200r-identifies-cells-involved-in-type-2-immune-responses
#15
Lars H Blom, Britta C Martel, Lau F Larsen, Camilla V Hansen, Malene P Christensen, Nanna Juel-Berg, Thomas Litman, Lars K Poulsen
BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim of this investigation was to identify surface markers associated with type 2 inflammation. METHODS: Naïve human CD4(+) T-cells were short-term activated in the presence or absence of IL-4, and analysed for expression of >300 cell-surface proteins...
January 20, 2017: Allergy
https://www.readbyqxmd.com/read/28097811/fc-silent-anti-cd154-domain-antibody-effectively-prevents-nonhuman-primate-renal-allograft-rejection
#16
S C Kim, W Wakwe, L B Higginbotham, D V Mathews, C P Breeden, A C Stephenson, J Jenkins, E Strobert, K Price, L Price, R Kuhn, H Wang, A Yamniuk, S Suchard, A B Farris, T C Pearson, C P Larsen, M L Ford, A Suri, S Nadler, A B Adams
The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004)...
May 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28093524/age-associated-b-cells-express-a-diverse-repertoire-of-vh-and-v%C3%AE%C2%BA-genes-with-somatic-hypermutation
#17
Lisa M Russell Knode, Martin S Naradikian, Arpita Myles, Jean L Scholz, Yi Hao, Danya Liu, Mandy L Ford, John W Tobias, Michael P Cancro, Patricia J Gearhart
The origin and nature of age-associated B cells (ABCs) in mice are poorly understood. In this article, we show that their emergence required MHC class II and CD40/CD40L interactions. Young donor B cells were adoptively transferred into congenic recipients and allowed to remain for 1 mo in the absence of external Ag. B cells expressing the T-bet transcription factor, a marker for ABCs, were generated after multiple cell divisions from C57BL/6 donors but not from MHC class II- or CD40-deficient donors. Furthermore, old CD154 (CD40L)-deficient mice did not accrue ABCs, confirming that they arise primarily through T-dependent interactions...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28058735/safe-use-of-anti-cd154-monoclonal-antibody-in-pig-islet-xenotransplantation-in-monkeys
#18
Rita Bottino, Michael F Knoll, Joshua Graeme-Wilson, Edwin C Klein, David Ayares, Massimo Trucco, David K C Cooper
Anti-CD154mAb is a powerful co-stimulation blockade agent that is efficacious in preventing rejection, even in xenogeneic settings. It has been used in the majority of successful long-term pig-to-non-human primate islet transplantation models. However, its clinical use was halted as a result of thromboembolic complications that were also observed in preclinical and clinical organ transplantation models. An anti-CD154mAb was administered to 14 streptozotocin-induced diabetic cynomolgus monkey recipients of porcine islets, some of which received the agent for many months...
January 2017: Xenotransplantation
https://www.readbyqxmd.com/read/27989689/cd40-signaling-and-hepatic-steatosis-unanticipated-links
#19
Sébastien Lepreux, Julien Villeneuve, Antoine Dewitte, Annie M Bérard, Alexis Desmoulière, Jean Ripoche
Obesity predisposes to an increased risk of nonalcoholic fatty liver disease (NAFLD). Hepatic steatosis is the key pathological feature of NAFLD and has emerged as a metabolic disorder in which innate and adaptive arms of the immune response play a central role in disease pathogenesis. Recent studies have revealed unexpected relationships between CD40 signaling and hepatic steatosis in high fat diet rodent models. CD154, the ligand of CD40, is a mediator of inflammation and controls several critical events of innate and adaptive immune responses...
December 15, 2016: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/27893093/ligation-of-cd40-in-human-m%C3%A3-ller-cells-induces-p2x7-receptor-dependent-death-of-retinal-endothelial-cells
#20
Jose-Andres C Portillo, Yalitza Lopez Corcino, George R Dubyak, Timothy S Kern, Shigemi Matsuyama, Carlos S Subauste
Purpose: Cluster of differentiation 40 (CD40) is required for retinal capillary degeneration in diabetic mice, a process mediated by the retinal endothelial cells (REC) death. However, CD40 activates prosurvival signals in endothelial cells. The purpose of this study was to identify a mechanism by which CD40 triggers programmed cell death (PCD) of RECs and address this paradox. Methods: Human RECs and Müller cells were incubated with CD154 and L-N6-(1-Iminoethyl)lysine (L-Nil, nitric oxide synthase 2 inhibitor), α-lipoic acid (inhibitor of oxidative stress), anti-Fas ligand antibody, or A-438079 (P2X7 adenosine triphosphate [ATP] receptor inhibitor)...
November 1, 2016: Investigative Ophthalmology & Visual Science
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