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European Journal of Immunology

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https://www.readbyqxmd.com/read/28426152/donor-specific-alloreactive-t-cells-can-be-quantified-from-whole-blood-and-may-predict-cellular-rejection-after-renal-transplantation
#1
Michaela Fischer, Sarah Leyking, Marco Schäfer, Julia Elsäßer, Martin Janssen, Janine Mihm, Kai van Bentum, Danilo Fliser, Martina Sester, Urban Sester
Preformed cellular alloreactivity can exist prior to transplantation and may contribute to rejection. Here, we used a rapid flow-cytometric whole-blood assay to characterize the extent of alloreactive T cells among 1491 stimulatory reactions from 61 renal transplant candidates and 75 controls. The role of preformed donor-specific alloreactive T cells in cellular rejection was prospectively analyzed in 21 renal transplant recipients. Alloreactive CD8(+) T cells were more frequent than respective CD4(+) T cells, and these levels were stable over time...
April 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28393361/immune-checkpoints-and-their-inhibition-in-cancer-and-infectious-diseases
#2
REVIEW
Lydia Dyck, Kingston H G Mills
The development of chronic infections and cancer is facilitated by a variety of immune subversion mechanisms, such as the production of anti-inflammatory cytokines, induction of regulatory T (Treg) cells and expression of immune checkpoint molecules, including CTLA-4 and PD-1. CTLA-4, expressed on T cells, interacts with CD80/CD86, thereby limiting T-cell activation and leading to anergy. PD-1 is predominantly expressed on T cells and its interaction with PD-L1 and PD-L2 expressed on antigen presenting cells (APCs) and tumours sends a negative signal to T cells, which can lead to T-cell exhaustion...
April 9, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386999/psoriatic-cutaneous-inflammation-promotes-human-monocyte-differentiation-into-active-osteoclasts-facilitating-bone-damage
#3
Annunziata Raimondo, Serena Lembo, Roberta Di Caprio, Giovanna Donnarumma, Giuseppe Monfrecola, Nicola Balato, Fabio Ayala, Anna Balato
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy that can be associated with focal bone erosions. Psoriasis usually precedes the psoriatic arthritis onset by an average of 10 years, but this relation is not yet fully elucidated. Pro-inflammatory cytokines, such as IL-33, OPN, IL-17 and TNF-α are involved in both psoriasis and PsA pathogenesis as well as in bone homeostasis. In this study, we have demonstrated that IL-33, OPN, IL-17 and TNF-α induced the release of a wide range of pro-osteoclastogenic factors from the skin, such as RANKL, that promote monocyte differentiation in osteoclasts...
April 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386934/eomes-expression-reports-the-progressive-differentiation-of-ifn-%C3%AE-producing-th1-like-%C3%AE-%C3%AE-t-cells
#4
Ciro N R Lino, Joana Barros-Martins, Linda Oberdörfer, Thierry Walzer, Immo Prinz
The transcription factor Eomesodermin (Eomes) plays a crucial role in regulating cytotoxic function, development and survival of immune cells. γδ T cells can express Eomes, but its contribution to their differentiation is unknown. Using Eomes-IRES-GFP mice, we show that Eomes(+) γδ T cells are unequally distributed among organs, with the highest proportion in spleen. While the majority of Eomes(+) γδ T cells expressed Vγ1(+) and Vγ4(+) TCRs, Eomes was absent in Vγ5(+) , Vγ6(+) and Vγ7(+) subsets...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386908/inhibitory-2b4-contributes-to-nk-cell-education-and-immunological-derangements-in-xlp1-patients
#5
Raffaella Meazza, Michela Falco, Stefania Marcenaro, Fabrizio Loiacono, Paolo Canevali, Francesca Bellora, Claudia Tuberosa, Franco Locatelli, Concetta Micalizzi, Alessandro Moretta, Maria C Mingari, Lorenzo Moretta, Maurizio Aricò, Cristina Bottino, Daniela Pende
X-linked lymphoproliferative disease 1 (XLP1) is an inherited immunodeficiency, caused by mutations in SH2D1A encoding Signaling Lymphocyte Activation Molecule (SLAM)-associated protein (SAP). In XLP1, 2B4, upon engagement with CD48, has inhibitory instead of activating function. This causes a selective inability of cytotoxic effectors to kill EBV-infected cells, with dramatic clinical sequelae. Here, we investigated the NK cell education in XLP1, upon characterization of KIR/KIR-L genotype and phenotypic repertoire of self-HLA class I specific inhibitory receptors (self-iNKR)...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28386905/butyrophilin-3a-btn3a-cd277-specific-antibody-20-1-differentially-activates-v%C3%AE-9v%C3%AE-2-tcr-clonotypes-and-interferes-with-phosphoantigen-activation
#6
Lisa Starick, Felipe Riano, Mohindar M Karunakaran, Volker Kunzmann, Jianqiang Li, Matthias Kreiss, Sabine Amslinger, Emmanuel Scotet, Daniel Olive, Gennaro De Libero, Thomas Herrmann
Phosphoantigens (PAg) like HMBPP ((E)-4-hydroxy-3-methyl-but-2-enyl diphosphate) and butyrophilin 3 (BTN3A, CD277)-specific monoclonal antibody (mAb) 20.1 induce TCR-mediated activation of Vγ9Vδ2 T cells. Here, we compared murine reporter cells transduced with Vγ9Vδ2 TCRs G115, D1C55 and MOP for the activation in culture with human RAJI cells and PAgs or mAb 20.1 and its single chain derivative (sc). All transductants responded readily to PAg but only TCR MOP γ-chain-expressing cells responded to mAb/sc 20...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28383780/immunoglobulin-superfamily-members-encoded-by-viruses-and-their-multiple-roles-in-immune-evasion
#7
REVIEW
Domènec Farré, Pablo Martínez-Vicente, Pablo Engel, Ana Angulo
Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily (IgSF), whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28383204/monocytic-myeloid-derived-suppressor-cells-regulate-t-cell-responses-against-vaccinia-virus
#8
Carl Fortin, Yiping Yang, Xiaopei Huang
Vaccinia virus (VV) can potently activate NK- and T-cell responses, leading to efficient viral control and generation of long-lasting protective immunity. However, immune responses against viral infections are often tightly controlled to avoid collateral damage and systemic inflammation. We have previously shown that granulocytic myeloid derived suppressor cells (g-MDSCs) can suppress the NK-cell response to VV infection. It remains unknown what regulates T-cell responses to VV infection in vivo. In this study, we first showed that monocytic MDSCs (m-MDSCs), but not g-MDSCs, from VV-infected mice could directly suppress CD4(+) and CD8(+) T-cell activation in vitro...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28383107/a-mouse-model-of-systemic-lupus-erythematosus-responds-better-to-soluble-taci-than-to-soluble-baffr-correlating-with-depletion-of-plasma-cells
#9
Philipp Haselmayer, Michele Vigolo, Josquin Nys, Pascal Schneider, Henry Hess
The TNF family cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR-Fc) or BAFF and APRIL (TACI-Fc) administered early enough in a NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI-Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28383105/enhancement-of-cytokine-driven-nk-cell-ifn-%C3%AE-production-after-vaccination-of-hcmv-infected-africans
#10
Alansana Darboe, Ebrima Danso, Ed Clarke, Ama Umesi, Ebrima Touray, Rita Wegmuller, Sophie E Moore, Eleanor M Riley, Martin R Goodier
Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28378389/nkg2d-stimulation-of-cd8-t-cells-during-priming-promotes-their-capacity-to-produce-cytokines-in-response-to-viral-infection-in-mice
#11
Inga Kavazović, Maja Lenartić, Vedrana Jelenčić, Slaven Jurković, Niels A W Lemmermann, Stipan Jonjić, Bojan Polić, Felix M Wensveen
NKG2D is an activating receptor that is expressed on most cytotoxic cells of the immune system, including NK cells, γδ and CD8(+) T cells. It is still a matter of debate whether and how NKG2D mediates priming of CD8(+) T cells in vivo, due to a lack of studies where NKG2D is eliminated exclusively in these cells. Here we studied the impact of NKG2D on effector CD8(+) T-cell formation. NKG2D-deficiency that is restricted to murine CD8(+) T cells did not impair antigen-specific T-cell expansion following mCMV and LCMV infection, but reduced their capacity to produce cytokines...
April 4, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28318017/thymic-crosstalk-restrains-the-pool-of-cortical-thymic-epithelial-cells-with-progenitor-properties
#12
Catarina Meireles, Ana R Ribeiro, Rute D Pinto, Catarina Leitão, Pedro M Rodrigues, Nuno L Alves
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs)...
March 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28303575/isoform-localization-of-dectin-1-regulates-the-signaling-quality-of-anti-fungal-immunity
#13
Mike Fischer, Jörg P Müller, Bärbel Spies-Weisshart, Christine Gräfe, Oliver Kurzai, Kerstin Hünniger, Andreas Hochhaus, Sebastian Scholl, Ulf Schnetzke
Dectin-1 is recognized as a major receptor for fungal ß-glucans and contributes to anti-fungal immunity. Human monocyte populations express Dectin-1 isoforms A and B, which differ by the presence of a stalk region and its N-linked glycosylation site. Here, we analyzed the expression of both isoforms in human monocyte-derived cells. The cellular localization on cell lines stably expressing either Dectin-1 isoform A or B was studied by flow cytometry and confocal laser scanning microscopy. Intracellular protein signaling and cytokine production were analyzed by immunoblotting and cytometric bead array, respectively...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28301039/bach2-regulates-aid-mediated-immunoglobulin-gene-conversion-and-somatic-hypermutation-in-dt40-b-cells
#14
Paulina M Budzyńska, Minna K Kyläniemi, Teemu Kallonen, Anni I Soikkeli, Kalle-Pekka Nera, Olli Lassila, Jukka Alinikula
The transcription factor Bach2 is required for germinal centre formation, somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28299776/toll-like-receptors-elicit-different-recruitment-kinetics-of-monocytes-and-neutrophils-in-mouse-acute-inflammation
#15
Beat A Imhof, Stephane Jemelin, Yalin Emre
Leukocyte recruitment is an important process in combating pathogens. The largest class of circulating leukocytes are neutrophils, which rapidly invade inflamed tissue, followed by inflammatory Ly6C(+) monocytes. Ly6C(low) monocytes patrol the endothelial wall routinely in the steady state. We recently reported early luminal recruitment of Ly6C(low) monocytes, which preceded and orchestrated neutrophil arrival and extravasation in response to TLR7/8-mediated vascular inflammation. Here we dissected the kinetics of recruitment of monocytes and neutrophils and examined the dynamics of Ly6C(low) monocytes in response to several other Toll-like receptor (TLR) agonists, using intravital confocal microscopy...
March 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295300/ifn-%C3%AE-directly-inhibits-murine-b-cell-precursor-leukemia-initiating-cell-proliferation-early-in-life
#16
Mario Fidanza, Alix E Seif, Sumin Jo, Amina Kariminia, Nina Rolf, Laura M Sly, Stephan A Grupp, Gregor S D Reid
The early-life immune environment has been implicated as a modulator of acute lymphoblastic leukemia (ALL) development in children, with infection being associated with significant changes in ALL risk. Furthermore, polymorphisms in several cytokine genes, including IL-10 and IFN-γ, are associated with leukemia development. However, the mechanisms and timing of these influences remain unknown. Here, we use the Eμ-ret transgenic mouse model of B-cell precursor ALL to assess the influence of IFN-γ on the early-life burden of leukemia-initiating cells...
March 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295238/il-17-and-il-22-in-immunity-driving-protection-and-pathology
#17
REVIEW
Eyerich Kilian, Dimartino Valentina, Cavani Andrea
IL-17 and IL-22 are tissue-signaling cytokines that favor protection and regeneration of barrier organs such as the skin, lung, and gastrointestinal system. Both cytokines share cellular sources, signaling pathways, and functional aspects; however, taking a closer look they differ, e.g. in their pro-inflammatory or regenerative potential. A dysbalance of the carefully orchestrated tissue-signaling system might result in autoimmune diseases, promote cancer growth, or predispose to infectious diseases. This review highlights recent understandings in cellular sources, signaling mechanisms, physiologic as well as pathogenic role of the double-faceted cytokines IL-17 and IL-22...
March 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295233/retention-of-ag-specific-memory-cd4-t-cells-in-the-draining-lymph-node-indicates-lymphoid-tissue-resident-memory-populations
#18
Clare L Marriott, Emma E Dutton, Michio Tomura, David R Withers
Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4(+) T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4(+) T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation...
March 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295265/card9-controls-dectin-1-induced-t-cell-cytotoxicity-and-tumor-growth-in-mice
#19
Haas Tobias, Heidegger Simon, Wintges Alexander, Bscheider Michael, Bek Sarah, Fischer Julius C, Eisenkolb Gabriel, Schmickl Martina, Spoerl Silvia, Peschel Christian, Poeck Hendrik, Ruland Jürgen
Activation of the C-type lectin receptor Dectin-1 by β-glucans triggers multiple signals within dendritic cells (DCs) that result in activation of innate immunity. While these mechanisms can potently prime CD8(+) cytotoxic T cell (CTL) responses without additional adjuvants, the Dectin-1 effector pathways that control CTL induction remain unclear. Here we demonstrate that Dectin-1-induced CTL cross-priming in mice does not require inflammasome activation but strictly depends on the adapter protein Card9 in vitro...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28295231/deficiency-in-irak4-activity-attenuates-manifestations-of-murine-lupus
#20
Michael Murphy, Goutham Pattabiraman, Tissa T Manavalan, Andrei E Medvedev
Interleukin-1 receptor-associated kinase (IRAK) 4 mediates host defense against infections. As an active kinase, IRAK4 elicits full spectra of myeloid differentiation primary response protein (MyD) 88-dependent responses, while kinase-inactive IRAK4 induces a subset of cytokines and negative regulators whose expression is not regulated by mRNA stability. IRAK4 kinase activity is critical for resistance against Streptococcus pneumoniae, but its involvement in autoimmunity is incompletely understood. In this study, we determined the role of IRAK4 kinase activity in murine lupus...
March 10, 2017: European Journal of Immunology
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