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https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#1
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28222841/phenotypic-and-functional-characterization-of-peripheral-blood-lymphocytes-from-various-age-and-sex-specific-groups-of-owl-monkeys-aotus-nancymaae
#2
Pramod N Nehete, Bharti P Nehete, Sriram Chitta, Lawrence E Williams, Christian R Abee
Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys...
February 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28219062/the-impact-on-allergy-related-cells-of-a-birch-pollen-allergoid-with-and-without-monophosphoryl-lipid-a-in-comparison-with-the-native-equivalent
#3
Margitta Worm, Dennis Ernst, Markus Kraller, Magda Babina
BACKGROUND: The clinical efficacy and safety of allergoid immunotherapy have been demonstrated in clinical trials. However, simultaneous monitoring of the immunological changes by allergoids versus allergens in the cells of the same individual has not been extensively performed, and the impact of concurrent Toll-like receptor 4 (TLR4) ligation has not been specified. METHODS: Three types of birch allergen were utilized: glutaraldehyde-treated allergoid (extract A), the same allergoid plus monophosphoryl lipid A (MPL), i...
February 21, 2017: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28216262/efis-lecture-understanding-the-ctla-4-checkpoint-in-the-maintenance-of-immune-homeostasis
#4
REVIEW
Lucy S K Walker
The past 20 years have heralded fascinating developments in the field of CTLA-4 biology. The CTLA-4 protein is a critical negative regulator of T cell immunity and its absence provokes severe lymphoproliferative disease. In a surprising twist, the generation of mixed bone marrow chimeric mice revealed that CTLA-4 predominantly functions in a cell-extrinsic manner, suggesting that CTLA-4 expressed on one cell can modify the behaviour of another cell. This was followed by the demonstration that CTLA-4 is highly expressed in regulatory T cells and can contribute to their suppressive activity...
February 16, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28215626/dendritic-cells-that-highly-express-socs1-induce-t-cell-hypo-responsiveness-and-prolong-islet-allograft-survival
#5
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/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#6
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28194020/cd103-lung-dendritic-cells-ldcs-induce-stronger-th1-th17-immunity-to-a-bacterial-lung-infection-than-cd11b-hi-ldcs
#7
Sudhanshu Shekhar, Ying Peng, Shuhe Wang, Xi Yang
Recent studies suggest differential roles for CD103+ and CD11b(hi) lung dendritic cells (LDCs) in host defense against viral and bacterial infections. In this study, we examined the contribution of these LDC subsets in protective immunity to chlamydial lung infection using a Chlamydia muridarum mouse infection model. We found that CD103+ LDCs showed higher expression of costimulatory molecules (CD40, CD80 and CD86) and increased production of cytokines (IL-12p70, IL-10, IL-23 and IL-6) compared with CD11b(hi) LDCs, but the expression of programmed death-ligand 1 (PD-L1) was similar between the two subsets...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28187172/generation-of-dendritic-cell-based-vaccine-using-high-hydrostatic-pressure-for-non-small-cell-lung-cancer-immunotherapy
#8
Nada Hradilova, Lenka Sadilkova, Ondrej Palata, Dagmar Mysikova, Hana Mrazkova, Robert Lischke, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h...
2017: PloS One
https://www.readbyqxmd.com/read/28186730/engineered-hydrogen-bonded-glycopolymer-capsules-and-their-interactions-with-antigen-presenting-cells
#9
Kristian Kempe, Sue D Xiang, Paul Wilson, Md Arifur Rahim, Yi Ju, Michael R Whittaker, David M Haddleton, Magdalena Plebanski, Frank Caruso, Thomas P Davis
Hollow glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)...
February 10, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28186428/eosinophils-regulate-interferon-alpha-production-in-plasmacytoid-dendritic-cells-stimulated-with-components-of-neutrophil-extracellular-traps
#10
Joanna Skrzeczynska-Moncznik, Katarzyna Zabieglo, Jozef P Bossowski, Oktawia Osiecka, Agnieszka Wlodarczyk, Monika Kapinska-Mrowiecka, Mateusz Kwitniewski, Pawel Majewski, Adam Dubin, Joanna Cichy
Eosinophils constitute an important component of helminth immunity and are not only associated with various allergies but are also linked to autoinflammatory disorders, including the skin disease psoriasis. Here we demonstrate the functional relationship between eosinophils and plasmacytoid dendritic cells (pDCs) as related to skin diseases. We previously showed that pDCs colocalize with neutrophil extracellular traps (NETs) in psoriatic skin. Here we demonstrate that eosinophils are found in psoriatic skin near neutrophils and NETs, suggesting that pDC responses can be regulated by eosinophils...
February 10, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28168174/sh2-domain-containing-adaptor-protein-b-expressed-in-dendritic-cells-is-involved-in-t-cell-homeostasis-by-regulating-dendritic-cell-mediated-th2-immunity
#11
Md Selim Ahmed, Myeong-Ho Kang, Ezra Lee, Yujin Park, Yideul Jeong, Yong-Soo Bae
PURPOSE: The Src homology 2 domain-containing adaptor protein B (SHB) is widely expressed in immune cells and acts as an important regulator for hematopoietic cell function. SHB silencing induces Th2 immunity in mice. SHB is also involved in T-cell homeostasis in vivo. However, SHB has not yet been studied and addressed in association with dendritic cells (DCs). MATERIALS AND METHODS: The effects of SHB expression on the immunogenicity of DCs were assessed by Shb gene silencing in mouse bone marrow-derived DCs (BMDCs)...
January 2017: Clinical and Experimental Vaccine Research
https://www.readbyqxmd.com/read/28165507/paeoniflorin-ameliorates-experimental-autoimmune-encephalomyelitis-via-inhibition-of-dendritic-cell-function-and-th17-cell-differentiation
#12
Han Zhang, Yuanyuan Qi, Yuanyang Yuan, Li Cai, Haiyan Xu, Lili Zhang, Bing Su, Hong Nie
Paeoniflorin (PF) is a monoterpene glycoside and exhibits multiple effects, including anti-inflammation and immunoregulation. To date, the effect of PF on multiple sclerosis (MS) has not been investigated. In this study, we investigated the effect of PF in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. After administered with PF, the onset and clinical symptoms of EAE mice were significantly ameliorated, and the number of Th17 cells infiltrated in central nervous system (CNS) and spleen was also dramatically decreased...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28160999/-the-immune-checkpoints-how-does-it-work
#13
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/28141831/b7-h3-augments-inflammatory-responses-and-exacerbates-brain-damage-via-amplifying-nf-%C3%AE%C2%BAb-p65-and-mapk-p38-activation-during-experimental-pneumococcal-meningitis
#14
Xuqin Chen, Yan Li, Siobhan Blankson, Min Liu, Danping Huang, H Paul Redmond, Jing Huang, Jiang Huai Wang, Jian Wang
The costimulatory protein B7-H3 has been shown to play a contributory role in the development and progression of experimental pneumococcal meningitis by augmentation of the innate immunity-associated inflammatory response via a TLR2-dependent manner. This study aimed to clarify the component(s) of TLR2-mediated signal transduction pathways responsible for B7-H3-augmented inflammatory response and subsequent brain damage during experimental pneumococcal meningitis. Administration of B7-H3 did not augment expression of TLR2 and other TLR2 upstream components, but led to an enhanced formation of MyD88-IRAK immunocomplex in the brain of S...
2017: PloS One
https://www.readbyqxmd.com/read/28127571/desensitization-overcoming-the-immunologic-barriers-to-transplantation
#15
REVIEW
Supreet Sethi, Jua Choi, Mieko Toyoda, Ashley Vo, Alice Peng, Stanley C Jordan
HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28120745/phenotypic-and-functional-characterization-of-peripheral-blood-lymphocytes-from-various-age-and-sex-specific-groups-of-owl-monkeys-aotus-nancymaae
#16
Pramod N Nehete Bharti P Nehete Sriram Chitta Lawrence E Williams And Christian R Abee
Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model forhuman disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys...
January 24, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28115358/therapeutic-efficacy-of-4-1bb-costimulation-is-abrogated-by-pd-1-blockade-in-a-model-of-spontaneous-b-cell-lymphoma
#17
Sara McKee, Brianna L Doff, Megan Sf Soon, Stephen R Mattarollo
Combinations of monoclonal antibodies (mAb) that target various components of T-cell activation/inhibition may work synergistically to improve antitumor immunity against cancer. In this study we investigated the therapeutic potential of combining an anticancer vaccination strategy with antibodies targeting an immune stimulatory (4-1BB) and immune inhibitory (PD-1) receptor, in a preclinical model of spontaneously arising c-Myc-driven B-cell lymphoma. In Eμ-myc transgenic mice we reveal that 4-1BB agonistic mAb treatment alone was sufficient to drive antitumor immunity and prevent disease progression in 70% of mice...
January 23, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28114251/novel-checkpoints-and-cosignaling-molecules-in-cancer-immunotherapy
#18
Iulia Giuroiu, Jeffrey Weber
The recent demonstration of the antitumor efficacy of checkpoint protein inhibition has resulted in the approval of blocking antibodies against the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway in multiple different histologic findings. Therapeutic successes with PD-1/PD-L1 antibodies in melanoma and lung cancer have been followed by approvals in bladder, renal, and head and neck cancers and Hodgkin lymphoma, with others undoubtedly to come. However, PD-1 is only one of many checkpoints and agonistic regulatory molecules expressed on T cells by which maintenance of the balance between costimulatory and coinhibitory signaling pathways is perturbed in cancer...
January 2017: Cancer Journal
https://www.readbyqxmd.com/read/28112644/pkc%C3%AE-links-proximal-t-cell-and-notch-signaling-through-localized-regulation-of-the-actin-cytoskeleton
#19
Graham J Britton, Rachel Ambler, Danielle J Clark, Elaine V Hill, Helen M Tunbridge, Kerrie E McNally, Bronwen R Burton, Philomena Butterweck, Catherine Sabatos-Peyton, Lea A Hampton-O'Neil, Paul Verkade, Christoph Wuelfing, David Cameron Wraith
Notch is a critical regulator of T cell differentiation and is activated through proteolytic cleavage in response to ligand engagement. Using murine myelin-reactive CD4 T cells, we demonstrate that proximal T cell signaling modulates Notch activation by a spatiotemporally constrained mechanism. The protein kinase PKCθ is a critical mediator of signaling by the T cell antigen receptor and the principal costimulatory receptor CD28. PKCθ selectively inactivates the negative regulator of F-actin generation, Coronin 1A, at the center of the T cell interface with the antigen presenting cell (APC)...
January 31, 2017: ELife
https://www.readbyqxmd.com/read/28108558/irf4-expression-in-thymic-epithelium-is-critical-for-thymic-regulatory-t-cell-homeostasis
#20
Uku Haljasorg, James Dooley, Martti Laan, Kai Kisand, Rudolf Bichele, Adrian Liston, Pärt Peterson
The thymus is a primary lymphoid organ required for the induction and maintenance of central tolerance. The main function of the thymus is to generate an immunocompetent set of T cells not reactive to self. During negative selection in the thymus, thymocytes with autoreactive potential are either deleted or differentiated into regulatory T cells (Tregs). The molecular basis by which the thymus allows high-efficiency Treg induction remains largely unknown. In this study, we report that IFN regulatory factor 4 (Irf4) is highly expressed in murine thymic epithelium and is required to prime thymic epithelial cells (TEC) for effective Treg induction...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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