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European Journal of Immunology

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https://www.readbyqxmd.com/read/28083937/type-1-diabetes-pathogenesis-is-modulated-by-spontaneous-autoimmune-responses-to-endogenous-retrovirus-antigens-in-nod-mice
#1
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
#2
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
#3
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
#4
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 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 to 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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28012163/il-10-production-in-murine-igm-cd138-hi-cells-is-driven-by-blimp1-and-downregulated-in-class-switched-cells
#8
Nao Suzuki-Yamazaki, Rieko Yanobu-Takanashi, Tadashi Okamura, Satoshi Takaki
In contrast to antibody-induced inflammatory responses, some B-cell subpopulations suppress inflammation through the production of interleukin (IL)-10. However, the mechanisms underlying Il10 gene expression during B-cell development is elusive. Here, we identify IgM(+) B220(lo) CD138(hi) cells responsible for marked IL-10 production in the bone marrow and spleen of mice. These murine IL-10-producing cells predominantly secrete IgM and have unique characteristics of long-lived plasma cells in spite of high expression of surface IgM...
December 23, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/28004382/help-to-go-t-cells-transfer-cd40l-to-antigen-presenting-b-cells
#9
Michael L Dustin
Most immune cell communication takes place by intercellular transfer of cytokines or the contact-dependent interaction of surface receptors in immunological synapses. In this issue of the European Journal of Immunology, Gardell and Parker (Eur. J. Immunol. 2016, X, XXX-XXX) point to a new, hybrid mechanism for Th1-cell delivery of help to B cells, based on contact-dependent CD40L transfer. The transfer process and its specificity are both cell contact dependent and antigen dependent. CD40 expression is also required on the B-cell surface to capture the CD40L presented by the Th1 cell...
December 22, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/28000923/core-principles-characterizing-immune-function
#10
Melvin Cohn
The immune system is an anticipatory mechanism designed by evolution to protect the individual against noxious agents and harmful cellular debris. In order to recognize substances that it has never encountered, the immune system somatically generates an appropriately sized random (with respect to self and nonself [NS]) recognitive repertoire that is coupled to a biodestructive and ridding output. Consequently, a Self-NS discrimination is required in order to avoid autoimmunity. This essay is an attempt to highlight the core principles upon which this anticipatory mechanism depends in order to function...
December 21, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27995616/b-cell-subsets-are-modulated-during-allergic-airway-inflammation-but-are-not-required-for-the-development-of-respiratory-tolerance-in-a-murine-model
#11
Anika Habener, Ann-Kathrin Behrendt, Jelena Skuljec, Adan Chari Jirmo, Almut Meyer-Bahlburg, Gesine Hansen
Allergic asthma is a widespread chronic inflammatory disease of the airways. The role of different B-cell subsets in developing asthma and respiratory tolerance is not well-known. Especially regulatory B (Breg) cells are proposed to be important in asthma regulation. Using wildtype (WT) and B-cell-deficient (μMT) mice we investigated how B-cells are affected by induction of allergic airway inflammation and respiratory tolerance and whether they are necessary to develop these conditions. WT mice with an asthma-like phenotype, characterized by increased airway hyperreactivity, eosinophilic airway inflammation, mucus hypersecretion and elevated Th2 cytokines, exhibited increased MHCII and CD23 expression on follicular mature B-cells in lung, bronchial lymph nodes (bLN) and spleen, which contributed to allergen-specific T-cell proliferation in vitro...
December 20, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27995614/influenza-and-dengue-virus-co-infection-impairs-monocyte-recruitment-to-the-lung-increases-dengue-virus-titers-and-exacerbates-pneumonia
#12
Michael A Schmid, Karla N González, Sanjana Shah, José Peña, Matthias Mack, Laura B Talarico, Fernando P Polack, Eva Harris
Co-infections of influenza virus and bacteria are known to cause severe disease, but little information exists on co-infections with other acute viruses. Seasonal influenza and dengue viruses (DENV) regularly co-circulate in tropical regions. The pandemic spread of influenza virus H1N1 (hereafter H1N1) in 2009 led to additional severe disease cases that were co-infected with DENV. Here, we investigated the impact of co-infection on immune responses and pathogenesis in a new mouse model. Co-infection of otherwise sublethal doses of a Nicaraguan clinical H1N1 isolate and two days later with a virulent DENV2 strain increased systemic DENV titers and caused 90% lethality...
December 20, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27995621/annexin-a1-promotes-timely-resolution-of-inflammation-in-murine-gout
#13
Izabela Galvão, Juliana P Vago, Livia C Barroso, Luciana P Tavares, Celso M Queiroz-Junior, Vivian V Costa, Fernanda S Carneiro, Tatiana P Ferreira, Patricia M R Silva, Flávio A Amaral, Lirlândia P Sousa, Mauro M Teixeira
Gout is a self-limited inflammatory disease caused by deposition of monosodium urate (MSU) crystals in the joints. Resolution of inflammation is an active process leading to restoration of tissue homeostasis. Here, we studied the role of Annexin A1 (AnxA1), a glucocorticoid-regulated protein that has anti-inflammatory and pro-resolving actions, in resolution of acute gouty inflammation. Injection of MSU crystals in the knee joint of mice induced inflammation that was associated with expression of AnxA1 during the resolving phase of inflammation...
December 19, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27995612/-inflamm-aging-influences-immune-cell-survival-factors-in-human-bone-marrow
#14
Luca Pangrazzi, Andreas Meryk, Erin Naismith, Rafal Koziel, Julian Lair, Martin Krismer, Klemens Trieb, Beatrix Grubeck-Loebenstein
The bone marrow (BM) plays a key role in the long-term maintenance of immunological memory. However, the impact of aging on the production of survival factors for effector/memory T cells and plasma cells in the human BM has not been studied. We now show that the expression of molecules involved in the maintenance of immunological memory in the human BM changes with age. While IL-15, which protects potentially harmful CD8(+) CD28(-) senescent T cells, increases, IL-7 decreases. IL-6, which may synergize with IL-15, is also overexpressed...
December 19, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27925658/pro-b-cells-propagated-in-stromal-cell-free-cultures-reconstitute-functional-b-cell-compartments-in-immunodeficient-mice
#15
Lilly von Muenchow, Panagiotis Tsapogas, Llucia Albertí-Servera, Giuseppina Capoferri, Marianne Doelz, Hannie Rolink, Nabil Bosco, Rhodri Ceredig, Antonius G Rolink
Up to now long-term in vitro growth of pro-B cells was thought to require stromal cells. However, here we show that fetal liver (FL) and bone marrow (BM) derived pro-B cells can be propagated long-term in stromal cell-free cultures supplemented with IL-7, stem cell factor and FLT3 ligand. Within a week, most cells expressed surface CD19, CD79A, λ5, and VpreB antigens and had rearranged immunoglobulin D-J heavy chain genes. Both FL and BM pro-B cells reconstituted the B-cell compartments of immuno-incompetent Rag2-deficient mice, with FL pro-B cells generating follicular, marginal zone (MZB) and B1a B cells, and BM pro-B cells giving rise mainly to MZB cells...
December 7, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27925643/primary-and-secondary-hemophagocytic-lymphohistiocytosis-have-different-patterns-of-t-cell-activation-differentiation-and-repertoire
#16
Sandra Ammann, Kai Lehmberg, Udo Zur Stadt, Gritta Janka, Anne Rensing-Ehl, Christian Klemann, Maximilian Heeg, Sebastian Bode, Ilka Fuchs, Stephan Ehl
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T-cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V-HLH). Polyclonal CD8(+) T cells are highly activated in 1°HLH and 2°V-HLH, but less in 2°HLH as assessed by HLA-DR expression and marker combination with CD45RA, CCR7, CD127, PD-1 and CD57...
December 7, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27910098/gata-3-specific-dnazyme-a-novel-approach-for-stratified-asthma-therapy
#17
REVIEW
Holger Garn, Harald Renz
It is now well established that type-2 immune mechanisms drive the inflammation in about 50% of asthma patients. The major cellular and molecular players regulating this important network have been identified. In terms of therapeutic intervention, cytokine and cytokine-receptor pathways have been given major attention, since these molecules are relatively easily accessible for a blockade through monoclonal antibodies, and a number of positive clinical results support this concept. However, targeting events controlling the type-2 immunity network upstream of selective cytokine pathways would be equally attractive...
December 2, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27891600/human-pdcs-display-sex-specific-differences-in-type-i-interferon-subtypes-and-interferon-%C3%AE-%C3%AE-receptor-expression
#18
Susanne M Ziegler, Claudia Beisel, Kathrin Sutter, Morgane Griesbeck, Heike Hildebrandt, Sven H Hagen, Ulf Dittmer, Marcus Altfeld
The outcomes of many diseases differ between women and men, with women experiencing a higher incidence and more severe pathogenesis of autoimmune and some infectious diseases. It has been suggested that this is partially due to activation of plasmacytoid dendritic cells (pDCs), the main producers of interferon (IFN)-α, in response to toll-like receptor (TLR)7 stimulation. We investigated the induction of type I IFN (IFN-I) subtypes upon TLR7 stimulation on isolated pDCs. Our data revealed a sex-specific differential expression of IFN-Is, with pDCs from females showing a significantly higher mRNA expression of all 13 IFN-α subtypes...
November 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27891580/acute-infection-with-the-intestinal-parasite-trichuris-muris-has-long-term-consequences-on-mucosal-mast-cell-homeostasis-and-epithelial-integrity
#19
Daniel Sorobetea, Jacob Bak Holm, Henrietta Henningsson, Karsten Kristiansen, Marcus Svensson-Frej
A hallmark of parasite infection is the accumulation of innate immune cells, notably granulocytes and mast cells, at the site of infection. While this is typically viewed as a transient response, with the tissue returning to steady state once the infection is cleared, we found that mast cells accumulated in the large-intestinal epithelium following infection with the nematode Trichuris muris and persisted at this site for several months after worm expulsion. Mast cell accumulation in the epithelium was associated with the induction of type-2 immunity and appeared to be driven by increased maturation of local progenitors in the intestinal lamina propria...
November 28, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27883180/mitochondrial-reactive-oxygen-species-suppress-humoral-immune-response-through-reduction-of-cd19-expression-in-b-cells-in-mice
#20
Masato Ogura, Takeshi Inoue, Junko Yamaki, Miwako K Homma, Tomohiro Kurosaki, Yoshimi Homma
Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A in B cells (bSDHA(Y215F) ). Splenic B cells in male, but not female, bSDHA(Y215F) mice produced three times more ROS than those in the control mice, and had decreased production of IgM, IgG1 , and IgG3 , and affinity maturation of IgG1 against T-cell-dependent antigens...
November 24, 2016: European Journal of Immunology
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