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Costimulatory t cells

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https://www.readbyqxmd.com/read/28427861/divergent-function-of-programmed-death-ligand-1-in-donor-tissue-versus-recipient-immune-system-in-a-murine-model-of-bronchiolitis-obliterans
#1
Katharina Schütte-Nütgen, Olaf Boenisch, Hakima Harrach, Alicia Casey, Indira Guleria, Nader Najafian, Mohamed H Sayegh, Craig J Gerard, Meera Subramaniam
Costimulatory molecules, such as the programmed death ligand (PD-L1), might exert differential effects on T-cell function, depending on the clinical setting and/or immunological environment. Given the impact of T cells on bronchiolitis obliterans (BO) in lung transplantation, we used an established tracheal transplant model inducing BO-like lesions to investigate the impact of PD-L1 on alloimmune responses and histopathological outcome in BO. In contrast to other transplant models in which PD-L1 generally shows protective functions, we demonstrated that PD-L1 has divergent effects depending on its location in donor versus recipient tissue...
April 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28421466/parathyroid-diseases-and-t-cells
#2
REVIEW
M Neale Weitzmann, Roberto Pacifici
PURPOSE OF REVIEW: This review summarizes studies into the permissive role of T cells in the bone catabolic effects of hyperparathyroidism and parathyroid hormone (PTH). RECENT FINDINGS: Work in animals combined with recent translational studies in humans now highlight the potent amplificatory action of T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a complex pathway by which PTH exploits natural self-renewal functions of CD4(+) T cells, to drive TNFα production that promotes formation of IL-17A secreting Th17 T cells...
April 18, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28415767/unique-properties-of-thymic-antigen-presenting-cells-promote-epigenetic-imprinting-of-alloantigen-specific-regulatory-t-cells
#3
Garima Garg, Eirini Nikolouli, Matthias Hardtke-Wolenski, Aras Toker, Naganari Ohkura, Michael Beckstette, Takahisa Miyao, Robert Geffers, Stefan Floess, Norbert Gerdes, Esther Lutgens, Anke Osterloh, Shohei Hori, Shimon Sakaguchi, Elmar Jaeckel, Jochen Huehn
Regulatory T cells (Tregs) are potential immunotherapeutic candidates to induce transplantation tolerance. However, stability of Tregs still remains contentious and may potentially restrict their clinical use. Recent work suggested that epigenetic imprinting of Foxp3 and other Treg-specific signature genes is crucial for stabilization of immunosuppressive properties of Foxp3+ Tregs, and that these events are initiated already during early stages of thymic Treg development. However, the mechanisms governing this process remain largely unknown...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408783/prokaryotic-expression-of-the-extracellular-domain-of-porcine-programmed-death-1-pd-1-and-its-ligand-pd-l1-and-identification-of-the-binding-with-peripheral-blood-mononuclear-cells-in-vitro
#4
Yan-Ping Zhu, Feng Yue, Yong He, Peng Li, Yuan Yang, Yu-Ting Han, Yan-Fang Zhang, Guo-Peng Sun, Dong-Guang Guo, Mei Yin, Xuan-Nian Wang
Programmed cell death protein 1 (PD-1), a costimulatory molecule of the CD28 family, has 2 ligands, PD-L1 and PD-L2. Our previous studies showed that the expression of PD-1 and PD-L1 is up-regulated during viral infection in pigs. Extensive studies have shown that blockade of the PD-1/PD-L1 pathways by anti-PD-L1 antibody or soluble PD-1 restores exhausted T-cells in humans and mice. In the present study the extracellular domains of PD-1 and PD-L1 were used to evaluate the binding of PD-1 and PD-L1 with peripheral blood mononuclear cells (PBMCs)...
April 2017: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
https://www.readbyqxmd.com/read/28404894/induction-and-characterization-of-anti-tumor-endothelium-immunity-elicited-by-vallovax-therapeutic-cancer-vaccine
#5
Samuel C Wagner, Thomas E Ichim, Vladimir Bogin, Wei-Ping Min, Francisco Silva, Amit N Patel, Santosh Kesari
ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28397730/programmed-cell-death-1-programmed-death-ligand-1-pathway-a-new-target-for-sepsis
#6
REVIEW
Qiang Liu, Chun-Sheng Li
OBJECTIVE: Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment...
April 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28396662/the-role-of-dendritic-cell-maturation-in-the-induction-of-insulin-dependent-diabetes-mellitus
#7
REVIEW
Jacques C Mbongue, Hector A Nieves, Timothy W Torrez, William H R Langridge
Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28395442/-pd-1-pd-l1-expression-and-its-implications-in-patients-with-chronic-lymphocytic-leukemia
#8
J H Li, N N Pang, Z H Zhang, R Zhang, G Chen, J H Qu
Objective: To observe the expression levels of PD-1/PD-L1 costimulatory molecules and explore the clinical significance in patients with chronic lymphocytic leukemia (CLL) . Methods: The expression of PD-1/PD-L1 in peripheral blood CD8(+) T cells, CD4(+)T cells, CD19(+)B, and dendrites cells (DC) was detected by flow cytometry in 57 CLL patients and 20 healthy controls. The correlations of PD-1/PD-L1 expression with disease stage, CD38 expression, ZAP-70 expression, chromosome karyotype abnormality and β(2)-MG expression were analyzed...
March 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28392507/gene-and-protein-expression-of-a-soluble-form-of-ctla-4-in-a-healthy-dog
#9
Michihito Tagawa, Yuhei Yamamoto, Genya Shimbo, Aiko Iguchi, Xuenan Xuan, Mizuki Tomihari, Kazuro Miyahara
Cytotoxic T lymphocyte associated gene-4 (CTLA-4) is a costimulatory molecule, expressed on the surface of activated T cells that negatively regulates T cell activation. In humans, alternative splicing of the CTLA-4 gene generates two major isoforms of mRNA, and a soluble form of CTLA-4 (sCTLA-4) was detected in normal human serum. We describe alternatively spliced mRNA expressed in peripheral blood mononuclear cells obtained from a healthy dog lacking the transmembrane domain coded by exon 3 of the CTLA-4 gene...
April 7, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28383653/immune-modulatory-micrornas-involved-in-tumor-attack-and-tumor-immune-escape
#10
Stefan B Eichmüller, Wolfram Osen, Ofer Mandelboim, Barbara Seliger
Current therapies against cancer utilize the patient's immune system for tumor eradication. However, tumor cells can evade immune surveillance of CD8+ T and/or natural killer (NK) cells by various strategies. These include the aberrant expression of human leukocyte antigen (HLA) class I antigens, co-inhibitory or costimulatory molecules, and components of the interferon (IFN) signal transduction pathway. In addition, alterations of the tumor microenvironment could interfere with efficient antitumor immune responses by downregulating or inhibiting the frequency and/or functional activity of immune effector cells and professional antigen-presenting cells...
April 5, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28378805/neonatal-mice-possess-two-phenotypically-and-functionally-distinct-lung-migratory-cd103-dendritic-cell-populations-following-respiratory-infection
#11
T J Ruckwardt, K M Morabito, E Bar-Haim, D Nair, B S Graham
The CD103(+) subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8(+) T cell responses following respiratory infection. Here, we demonstrate that the dependence on CD103(+) DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103(+) DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103(+) DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28369782/immune-checkpoint-proteins-exploring-their-therapeutic-potential-to-regulate-atherosclerosis
#12
REVIEW
A C Foks, J Kuiper
The immune system provides a large diversity of immune checkpoint proteins, which involve both costimulatory and inhibitory proteins. Costimulatory proteins can promote cell survival, cell cycle progression and differentiation to effector and memory cells, whereas inhibitory proteins terminate these processes to halt ongoing inflammation. Immune checkpoint proteins play a pivotal role in atherosclerosis by regulating the activation and proliferation of various immune and non-immune cells, such as T cells, macrophages and platelets...
March 30, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28363907/retinoic-acid-regulates-immune-responses-by-promoting-il-22-and-modulating-s100-proteins-in-viral-hepatitis
#13
Zuliang Jie, Yuejin Liang, Panpan Yi, Hui Tang, Lynn Soong, Yingzi Cong, Kangling Zhang, Jiaren Sun
Although large amounts of vitamin A and its metabolite all-trans retinoic acid (RA) are stored in the liver, how RA regulates liver immune responses during viral infection remains unclear. In this study, we demonstrated that IL-22, mainly produced by hepatic γδ T cells, attenuated liver injury in adenovirus-infected mice. RA can promote γδ T cells to produce mTORC1-dependent IL-22 in the liver, but inhibits IFN-γ and IL-17. RA also affected the aptitude of T cell responses by modulating dendritic cell (DC) migration and costimulatory molecule expression...
March 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28360089/atvb-distinguished-scientist-award-how-costimulatory-and-coinhibitory-pathways-shape-atherosclerosis
#14
REVIEW
Klaus Ley, Norbert Gerdes, Holger Winkels
OBJECTIVE: Immune cells play a critical role in atherosclerosis. Costimulatory and coinhibitory molecules of the tumor necrosis factor receptor and CD28 immunoglobulin superfamilies not only shape T-cell and B-cell responses but also have a major effect on antigen-presenting cells and nonimmune cells. APPROACH AND RESULTS: Pharmacological inhibition or activation of costimulatory and coinhibitory molecules and genetic deletion demonstrated their involvement in atherosclerosis...
March 30, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28355607/superagonistic-cd28-protects-against-renal-ischemic-injury-by-expansion-of-regulatory-t-cell
#15
Yiran Liang, Yan Li, Qing Kuang, Xiaoqiang Ding, Zheng Wei, Yi Fang
BACKGROUND: Regulatory T (Treg) cells are a highly suppressive subset of CD4+ lymphocytes and have recently been proved to be crucial to suppress the inflammatory responses of ischemic kidney injury. CD28 superagonists (CD28sa) are monoclonal antibodies that preferentially expand Treg cells without a T-cell receptor and a costimulatory signal. This study aims to test the protection and discover the mechanisms of CD28sa treatment against renal ischemia-reperfusion (IR) injury (IRI). METHODS: Male C57BL/6N mice were treated with CD28sa via peritoneal injection (0...
March 29, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#16
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28343701/toll-like-receptor-8-agonist-nanoparticles-mimic-immunomodulating-effects-of-the-live-bcg-vaccine-and-enhance-neonatal-innate-and-adaptive-immune-responses
#17
David J Dowling, Evan A Scott, Annette Scheid, Ilana Bergelson, Sweta Joshi, Carlo Pietrasanta, Spencer Brightman, Guzman Sanchez-Schmitz, Simon D Van Haren, Jana Ninković, Dina Kats, Cristiana Guiducci, Alexandre de Titta, Daniel K Bonner, Sachiko Hirosue, Melody A Swartz, Jeffrey A Hubbell, Ofer Levy
BACKGROUND: Newborns display distinct immune responses, leaving them vulnerable to infections and impairing immunization. Targeting newborn dendritic cells (DCs), which integrate vaccine signals into adaptive immune responses, might enable development of age-specific vaccine formulations to overcome suboptimal immunization. OBJECTIVE: Small-molecule imidazoquinoline Toll-like receptor (TLR) 8 agonists robustly activate newborn DCs but can result in reactogenicity when delivered in soluble form...
March 14, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28341666/pd-1-blockade-mediated-rescue-of-exhausted-t-cells-requires-cd28
#18
(no author information available yet)
PD-1 suppresses T cell activity by inhibiting the T cell costimulatory receptor CD28.
March 24, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28337196/salmonella-typhi-porins-ompc-and-ompf-are-potent-adjuvants-for-t-dependent-and-t-independent-antigens
#19
Marisol Pérez-Toledo, Nuriban Valero-Pacheco, Rodolfo Pastelin-Palacios, Cristina Gil-Cruz, Christian Perez-Shibayama, Mario A Moreno-Eutimio, Ingeborg Becker, Sonia Mayra Pérez-Tapia, Lourdes Arriaga-Pizano, Adam F Cunningham, Armando Isibasi, Laura C Bonifaz, Constantino López-Macías
Several microbial components, such as bacterial DNA and flagellin, have been used as experimental vaccine adjuvants because of their inherent capacity to efficiently activate innate immune responses. Likewise, our previous work has shown that the major Salmonella Typhi (S. Typhi) outer membrane proteins OmpC and OmpF (porins) are highly immunogenic protective antigens that efficiently stimulate innate and adaptive immune responses in the absence of exogenous adjuvants. Moreover, S. Typhi porins induce the expression of costimulatory molecules on antigen-presenting cells through toll-like receptor canonical signaling pathways...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28321220/adjusted-particle-size-eliminates-the-need-of-linkage-of-antigen-and-adjuvants-for-appropriated-t-cell-responses-in-virus-like-particle-based-vaccines
#20
Ariane C Gomes, Anna Flace, Philippe Saudan, Franziska Zabel, Gustavo Cabral-Miranda, Aadil El Turabi, Vania Manolova, Martin F Bachmann
Since the discovery of the first virus-like particle (VLP) derived from hepatitis B virus in 1980 (1), the field has expanded substantially. Besides successful use of VLPs as safe autologous virus-targeting vaccines, the powerful immunogenicity of VLPs has been also harnessed to generate immune response against heterologous and even self-antigens (2-4). Linking adjuvants to VLPs displaying heterologous antigen ensures simultaneous delivery of all vaccine components to the same antigen-presenting cells. As a consequence, antigen-presenting cells, such as dendritic cells, will process and present the antigen displayed on VLPs while receiving costimulatory signals by the VLP-incorporated adjuvant...
2017: Frontiers in Immunology
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