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European Journal of Immunology

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https://www.readbyqxmd.com/read/28198545/the-therapeutic-t-cell-response-induced-by-tumor-delivery-of-tnf-and-melphalan-is-dependent-on-early-triggering-of-natural-killer-and-dendritic-cells
#1
Enrica Balza, Silvia Zanellato, Alessandro Poggi, Daniele Reverberi, Anna Rubartelli, Lorenzo Mortara
The fusion protein L19mTNF (mouse TNF and human antibody fragment L19 directed to fibronectin extra domain-B) selectively targets the tumor vasculature, and in combination with melphalan induces a long-lasting T-cell therapeutic response and immune memory in murine models. Increasing evidence suggests that natural killer (NK) cells act to promote effective T-cell-based antitumor responses. We have analyzed the role of NK cells and dendritic cells (DCs) on two different murine tumor models: WEHI-164 fibrosarcoma and C51 colon carcinoma, in which the combined treatment induces high and low rejection rates respectively...
February 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28198542/ceramide-synthase-2-facilitates-s1p-dependent-egress-of-thymocytes-into-the-circulation-in-mice
#2
Michael Rieck, Christiane Kremser, Katarzyna Jobin, Elisabeth Mettke, Christian Kurts, Markus Gräler, Klaus Willecke, Waldemar Kolanus
Well-defined gradients of the lipid mediator sphingosine-1-phosphate (S1P) direct chemotactic egress of mature thymocytes from the thymus into the circulation. Although it is known that these gradients result from low S1P levels in the thymic parenchyma and high S1P concentrations at the exit sites and in the plasma, the biochemical mechanisms that regulate these differential S1P levels remain unclear. Several studies demonstrated that ceramide synthase 2 (Cers2) regulates the levels of the S1P precursor sphingosine...
February 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28191644/nk-cell-receptors-nkp46-and-ncr1-control-human-metapneumovirus-infection
#3
Mohammad Diab, Ariella Glasner, Batya Issacson, Yotam Bar-On, Yaron Drori, Rachel Yamin, Alexandra Duev-Cohen, Oded Danziger, Rachel Zamostiano, Michal Mandelboim, Stipan Jonjic, Eran Bacharach, Ofer Mandelboim
Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46 activating receptor and its mouse orthologue Ncr1, both members of the NCR family, recognized an unknown ligand expressed by HMPV infected human cells...
February 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28191643/cd11b-regulates-via-il-6-the-treg-th17-balance-in-murine-arthritis
#4
Mathias Stevanin, Nathalie Busso, Veronique Chobaz, Matteo Pigni, Sahar Ghassem-Zadeh, Li Zhang, Hans Acha-Orbea, Driss Ehirchiou
Th17 cells are often associated with autoimmunity and been shown to be increased in CD11b(-/-) mice. Here, we examined the role of CD11b in murine collagen-induced arthritis (CIA)-induced arthritis. C57BL/6 and CD11b(-/-) resistant mice were immunized with type II collagen. CD11b(-/-) mice developed arthritis with early onset, high incidence and sustained severity compared with C57BL/6 mice. We observed a marked leukocyte infiltration, and histological examinations of the arthritic paws from CD11b(-/-) mice revealed that the cartilage was destroyed in association with strong lymphocytic infiltration...
February 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28155222/skewing-towards-treg-and-th2-responses-is-a-characteristic-feature-of-sustained-remission-in-anca-positive-granulomatosis-with-polyangiitis
#5
Wojciech Szczeklik, Bogdan Jakieła, Katarzyna Wawrzycka-Adamczyk, Marek Sanak, Magdalena Hubalewska-Mazgaj, Agnieszka Padjas, Marcin Surmiak, Katarzyna Szczeklik, Jan Sznajd, Jacek Musiał
The objective of our study was to evaluate the T-helper (Th) and regulatory T (Treg) cell profile in ANCA-positive granulomatosis with polyangiitis (GPA) and its relation to disease activity. In a prospective study, we studied two groups of GPA patients: (1) disease flare (active-GPA, BVAS>6, n = 19), (2) sustained remission (≥ 1-year prior enrollment, inactive-GPA, BVAS = 0, n = 18). 24 age-sex matched healthy subjects served as controls. Active-GPA patients were followed for 6 months and reevaluated during remission (early remission; n = 13)...
February 2, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28150302/immunological-consequences-of-strain-variation-within-the-mycobacterium-tuberculosis-complex
#6
Leopold D Tientcheu, Anastasia Koch, Mthawelenga Ndengane, Genevieve Andoseh, Beate Kampmann, Robert J Wilkinson
In 2015 there were an estimated 10.4 million new cases of Tuberculosis (TB) globally, making it one of the leading causes of death due to an infectious disease. TB is caused by members of the Mycobacterium tuberculosis complex (MTBC), with human disease resulting from infection by M. tuberculosis sensu strico and M. africanum. Recent progress in genotyping techniques, in particular the increasing availability of whole genome sequence data, has revealed previously under appreciated levels of genetic diversity within the MTBC...
February 2, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28127757/donor-bone-marrow-cells-are-essential-for-inkt-cell-mediated-foxp3-treg-cell-expansion-in-a-murine-model-of-transplantation-tolerance
#7
Satoshi Miyairi, Toshihito Hirai, Rumi Ishii, Masayoshi Okumi, Shinichi Nunoda, Kenji Yamazaki, Yasuyuki Ishii, Kazunari Tanabe
Mixed chimerism induction is the most reliable method for establishing transplantation tolerance. We previously described a novel treatment using a suboptimal dose of anti-CD40 ligand (anti-CD40L) and liposomal formulation of a ligand for invariant natural killer T cells administered to sub-lethally irradiated recipient mice after donor bone marrow cell (BMC) transfer. Recipient mice treated with this regimen showed expansion of a Foxp3-positive regulatory T(Treg) cell phenotype, and formation of mixed chimera...
January 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28127756/absence-of-dcir1-reduces-the-mortality-rate-of-endotoxemic-hepatitis-in-mice
#8
Toshifumi Ishiguro, Testuya Fukawa, Kotaro Akaki, Koji Nagaoka, Tatsuki Takeda, Yoichiro Iwakura, Kayo Inaba, Kazuhiko Takahara
Dendritic cell immunoreceptor (DCIR) is a C-type lectin with an immunoreceptor tyrosine-based inhibitory motif (ITIM). Mice lacking DCIR1 (Dcir1(-/-) mice) show higher susceptibility to chronic arthritis with increasing age, suggesting that DCIR1 is involved in immune modulation via its ITIM. However, the role of DCIR1 in acute immune responses is not clear. In this study, we explored its role in acute experimental hepatitis. Upon injection of d-galactosamine and lipopolysaccharide, Dcir1(-/-) mice showed decreased mortality rates and serum levels of alanine aminotransferase (ALT)...
January 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28105679/robust-immunoglobulin-class-switch-recombination-and-end-joining-in-parp9-deficient-mice
#9
Isabelle Robert, Léa Gaudot, Jose Yelamos, Aurélia Noll, Heng-Kuan Wong, Françoise Dantzer, Valérie Schreiber, Bernardo Reina-San-Martin
To mount highly specific and adapted immune responses, B lymphocytes assemble and diversify their antibody repertoire through mechanisms involving the formation of programmed DNA damage. Immunoglobulin class switch recombination (CSR) is triggered by DNA lesions induced by activation-induced cytidine deaminase, which are processed to double-stranded DNA break (DSB) intermediates. These DSBs activate the cellular DNA damage response and enroll numerous DNA repair factors, involving Poly(ADP-ribose) polymerases Parp1, Parp2 and Parp3 to promote appropriate DNA repair and efficient long-range recombination...
January 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28105653/properdin-and-factor-h-production-by-human-dendritic-cells-modulates-their-t-cell-stimulatory-capacity-and-is-regulated-by-ifn-%C3%AE
#10
Karen O Dixon, Joseph O'Flynn, Ngaisah Klar-Mohamad, Mohamed R Daha, Cees van Kooten
Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T-cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs...
January 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28102569/human-%C3%AE-defensin-3-increases-the-tlr9-dependent-response-to-bacterial-dna
#11
Sarah L McGlasson, Fiona Semple, Heather MacPherson, Mohini Gray, Donald J Davidson, Julia R Dorin
Human β-defensin 3 (hBD3) is a cationic antimicrobial peptide with potent bactericidal activity in vitro. HBD3 is produced in response to pathogen challenge and can modulate immune responses. The amplified recognition of self-DNA by human plasmacytoid dendritic cells has been previously reported, but we show here that hBD3 preferentially enhances the response to bacterial DNA in mouse Flt-3 induced dendritic cells (FLDCs) and in human peripheral blood mononuclear cells. We show the effect is mediated through TLR9 and although hBD3 significantly increases the cellular uptake of both E...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28102541/tgf-%C3%AE-regulation-of-encephalitogenic-and-regulatory-t-cells-in-multiple-sclerosis
#12
Priscilla W Lee, Mary E Severin, Amy E Lovett-Racke
Transforming growth factor beta (TGF-β) is a pleiotropic cytokine that has been shown to influence the differentiation and function of T cells. The role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area of investigation since CD4(+) T cells appear to be a major mediator of autoimmunity. This review provides an analysis of the literature on the role that TGF-β plays in the generation and regulation of encephalitogenic and regulatory T cells (Treg) in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as well as in T cells of MS patients...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28101913/nasopharyngeal-colonization-with-streptococcus-pneumoniae-triggers-dendritic-cell-dependent-antibody-responses-against-invasive-disease-in-mice
#13
Anne Dommaschk, Nadine Ding, Meritxell Tort Tarres, Lara F Bittersohl, Regina Maus, Jennifer Stolper, Danny Jonigk, Peter Braubach, Torsten Lippmann, Tobias Welte, Ulrich A Maus
Nasopharyngeal colonization with Streptococcus pneumoniae (Spn) is an important precondition for the development of pneumococcal pneumonia. At the same time, nasopharyngeal colonization with Spn has been shown to mount adaptive immune responses against Spn in mice and humans. Cellular responses of the nasopharyngeal compartment, including the nasal-associated lymphoid tissue, to pneumococcal colonization and their importance for developing adaptive immune responses are poorly defined. We show that nasopharyngeal colonization with S...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28083937/type-1-diabetes-pathogenesis-is-modulated-by-spontaneous-autoimmune-responses-to-endogenous-retrovirus-antigens-in-nod-mice
#14
Roman Bashratyan, Danielle Regn, M Jubayer Rahman, Kristi Marquardt, Elizabeth Fink, Wen-Yuan Hu, John H Elder, James Binley, Linda A Sherman, Yang D Dai
Secreted microvesicles (MVs) are potent inflammatory triggers that stimulate autoreactive B and T cells, causing Type 1 Diabetes in non-obese diabetic (NOD) mice. Proteomic analysis of purified MVs released from islet cells detected the presence of endogenous retrovirus (ERV) antigens, including Env and Gag sequences similar to the well-characterized murine leukemia retroviruses. This raises the possibility that ERV antigens may be expressed in the pancreatic islets via MV secretion. Using virus-like particles produced by co-expressing ERV Env and Gag antigens, and a recombinant gp70 Env protein, we demonstrated that NOD but not diabetes-resistant mice developed anti-Env autoantibodies that increase in titer as disease progresses...
January 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28083930/functional-and-structural-characterization-of-four-mouse-monoclonal-antibodies-to-complement-c3-with-potential-therapeutic-and-diagnostic-applications
#15
Marta Subías Hidalgo, Hugo Yébenes, César Rodríguez-Gallego, Adrián Martín-Ambrosio, Mercedes Domínguez, Agustin Tortajada, Santiago Rodríguez de Córdoba, Oscar Llorca
C3 is the central component of the complement system. Upon activation, C3 sequentially generates various proteolytic fragments, C3a, C3b, iC3b, C3dg, each of them exposing novel surfaces, which are sites of interaction with other proteins. C3 and its fragments are therapeutic targets and markers of complement activation. We report the structural and functional characterization of four monoclonal antibodies (mAbs) generated by immunizing C3-deficient mice with a mixture of human C3b, iC3b and C3dg fragments, and discuss their potential applications...
January 13, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28078715/mtorc2-regulates-multiple-aspects-of-nkt-cell-development-and-function
#16
Tammarah Sklarz, Peng Guan, Mercy Gohil, Renee M Cotton, Moyar Q Ge, Angela Haczku, Rupali Das, Martha S Jordan
Invariant NKT (iNKT) cells bridge innate and adaptive immunity by rapidly secreting cytokines and lysing targets following TCR recognition of lipid antigens. Based on their ability to secrete IFN-γ, IL-4 and IL-17A, iNKT-cells are classified as NKT-1, NKT-2, and NKT-17 subsets, respectively. The molecular pathways regulating iNKT-cell fate are not fully defined. Recent studies implicate Rictor, a required component of mTORC2, in the development of select iNKT-cell subsets, however these reports are conflicting...
January 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28058717/deletional-tolerance-prevents-aqp4-directed-autoimmunity-in-mice
#17
Anna-Lena Vogel, Benjamin Knier, Katja Lammens, Sudhakar Reddy Kalluri, Tanja Kuhlmann, Jeffrey L Bennett, Thomas Korn
Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system (CNS) mediated by antibodies to the water channel protein AQP4 expressed in astrocytes. The contribution of AQP4-specific T cells to the class switch recombination of pathogenic AQP4-specific antibodies and the inflammation of the blood-brain barrier is incompletely understood, as immunogenic naturally processed T-cell epitopes of AQP4 are unknown. By immunizing Aqp4(-/-) mice with full-length murine AQP4 protein followed by recall with overlapping peptides, we here identify AQP4(201-220) as the major immunogenic IA(b) -restricted epitope of AQP4...
January 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28054344/nutritional-effects-on-t-cell-immunometabolism
#18
Sivan Cohen, Keiko Danzaki, Nancie J MacIver
T cells are highly influenced by nutrient uptake from their environment, and changes in overall nutritional status, such as malnutrition or obesity, can result in altered T-cell metabolism and behavior. In states of severe malnutrition or starvation, T-cell survival, proliferation, and inflammatory cytokine production are all decreased, as is T-cell glucose uptake and metabolism. The altered T-cell function and metabolism seen in malnutrition is associated with altered adipokine levels, most particularly decreased leptin...
January 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28012172/mhc-class-ii-alleles-associated-with-th1-rather-than-th17-type-immunity-drive-the-onset-of-early-arthritis-in-a-rat-model-of-rheumatoid-arthritis
#19
Jonatan Tuncel, Sabrina Haag, Rikard Holmdahl
Polymorphisms in the MHC class II (MHCII) genes are strongly associated with rheumatoid arthritis, supporting the importance of autoreactive T helper (Th) cells for the development of this disease. Here, we used pristane-induced arthritis (PIA), induced by the non-antigenic hydrocarbon pristane, to study the impact of different MHCII alleles on T-cell activation and differentiation. In MHCII-congenic rats with disease-promoting MHCII alleles, pristane primarily induced activation of Th1 cells, whereas activated T cells were Th17 biased in rats with protective MHCII alleles...
December 24, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/28012161/preferentially-expanding-v%C3%AE-1-%C3%AE-%C3%AE-t-cells-are-associated-with-protective-immunity-against-plasmodium-infection-in-mice
#20
Shin-Ichi Inoue, Mamoru Niikura, Hiroko Asahi, Yoichiro Iwakura, Yasushi Kawakami, Fumie Kobayashi
γδ T cells play a crucial role in controlling malaria parasites. Dendritic cell (DC) activation via CD40 ligand (CD40L)-CD40 signalling by γδ T cells induces protective immunity against the blood-stage Plasmodium berghei XAT (PbXAT) parasites in mice. However, it is unknown which γδ T-cell subset has an effector role and is required to control the Plasmodium infection. Here, using antibodies to deplete TCR Vγ1(+) cells, we saw that Vγ1(+) γδ T cells were important for the control of PbXAT infection...
December 24, 2016: European Journal of Immunology
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