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Clinical & Translational Immunology

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https://www.readbyqxmd.com/read/28265374/erratum-mait-cells-new-guardians-of-the-liver
#1
Ayako Kurioka, Lucy J Walker, Paul Klenerman, Christian B Willberg
[This corrects the article DOI: 10.1038/cti.2016.51.].
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28265373/a-generalized-quantitative-antibody-homeostasis-model-regulation-of-b-cell-development-by-bcr-saturation-and-novel-insights-into-bone-marrow-function
#2
József Prechl
In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this first paper, we describe the cycles of B-cell expansion and differentiation driven by B-cell receptor engagement. The fate of a B cell is determined by the signals it receives via its antigen receptor at any point of its lifetime. We express BCR engagement as a function of apparent affinity and free antigen concentration, using the range of 10(-14)-10(-3) M for both factors...
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28243438/roles-of-the-intestinal-microbiota-in-pathogen-protection
#3
REVIEW
Carles Ubeda, Ana Djukovic, Sandrine Isaac
Hundreds of commensal bacterial species inhabit the gastrointestinal tract. This diverse microbial ecosystem plays a crucial role in the prevention and resolution of infectious diseases. In this review we will describe the major mechanisms by which the intestinal microbiota confers protection against infections, focusing on those caused by intestinal bacterial pathogens. These mechanisms include both non-immune- and immune-cell-mediated pathways, notably through bacterial production of inhibitory molecules and nutrient deprivation by the former and innate lymphoid cell-, myeloid cell- or lymphocyte-dependent stimulation by the latter...
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28243437/analysis-of-the-cross-talk-of-epstein-barr-virus-infected-b-cells-with-t-cells-in-the-marmoset
#4
Jordon Dunham, Nikki van Driel, Bart Jl Eggen, Chaitali Paul, Bert A 't Hart, Jon D Laman, Yolanda S Kap
Despite the well-known association of Epstein-Barr virus (EBV), a lymphocryptovirus (LCV), with multiple sclerosis, a clear pathogenic role for disease progression has not been established. The translationally relevant experimental autoimmune encephalomyelitis (EAE) model in marmoset monkeys revealed that LCV-infected B cells have a central pathogenic role in the activation of T cells that drive EAE progression. We hypothesized that LCV-infected B cells induce T-cell functions relevant for EAE progression. In the current study, we examined the ex vivo cross-talk between lymph node mononuclear cells (MNCs) from EAE marmosets and (semi-) autologous EBV-infected B-lymphoblastoid cell lines (B-LCLs)...
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28197337/defective-t-cell-control-of-epstein-barr-virus-infection-in-multiple-sclerosis
#5
Michael P Pender, Peter A Csurhes, Jacqueline M Burrows, Scott R Burrows
Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8(+) T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28197336/embracing-the-gut-microbiota-the-new-frontier-for-inflammatory-and-infectious-diseases
#6
REVIEW
Lieke Wj van den Elsen, Hazel C Poyntz, Laura S Weyrich, Wayne Young, Elizabeth E Forbes-Blom
The gut microbiota provides essential signals for the development and appropriate function of the immune system. Through this critical contribution to immune fitness, the gut microbiota has a key role in health and disease. Recent advances in the technological applications to study microbial communities and their functions have contributed to a rapid increase in host-microbiota research. Although it still remains difficult to define a so-called 'normal' or 'healthy' microbial composition, alterations in the gut microbiota have been shown to influence the susceptibility of the host to different diseases...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28197335/caspase-8-not-so-silently-deadly
#7
REVIEW
Rebecca Feltham, James E Vince, Kate E Lawlor
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090323/high-thioredoxin-1-levels-in-rheumatoid-arthritis-patients-diminish-binding-and-signalling-of-the-monoclonal-antibody-tregalizumab
#8
Katharina Heim, Benjamin Dälken, Stefanie Faust, Faiza Rharbaoui, Andre Engling, Holger Wallmeier, Theodor Dingermann, Heinfried H Radeke, Jörg Schüttrumpf, Marcus Gutscher
The humanized non-depleting anti-CD4 monoclonal antibody Tregalizumab (BT-061) is able to selectively activate the suppressive function of regulatory T cells and has been investigated up to phase IIb in clinical trials in patients suffering from rheumatoid arthritis (RA). A pharmacokinetic-pharmacodynamic model based on clinical data from RA and healthy volunteers, which used the cell surface CD4 downmodulation as marker of activity, confirmed a stronger effect in healthy volunteers compared with RA patients...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090322/vaccination-to-gain-humoral-immune-memory
#9
REVIEW
Jana Sarkander, Shintaro Hojyo, Koji Tokoyoda
The concept of immune memory forms the biological basis for vaccination programs. Despite advancements in the field of immune memory and vaccination, most current vaccines are evaluated by magnitude of antigen-specific antibody titers in serum or mucosa after vaccination. It has been shown, however, that antibody-mediated humoral immune memory is established regardless of the magnitude and duration of immune reactions, suggesting that assessment of vaccine efficacy should be performed for several years after vaccination...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090321/gm-csf-signalling-blockade-and-chemotherapeutic-agents-act-in-concert-to-inhibit-the-function-of-myeloid-derived-suppressor-cells-in-vitro
#10
Tessa Gargett, Susan N Christo, Timothy R Hercus, Nazim Abbas, Nimit Singhal, Angel F Lopez, Michael P Brown
Immune evasion is a recently defined hallmark of cancer, and immunotherapeutic approaches that stimulate an immune response to tumours are gaining recognition. However tumours may evade the immune response and resist immune-targeted treatment by promoting an immune-suppressive environment and stimulating the differentiation or recruitment of immunosuppressive cells. Myeloid-derived suppressor cells (MDSC) have been identified in a range of cancers and are often associated with tumour progression and poor patient outcomes...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090320/immunopathogenesis-of-granulomas-in-chronic-autoinflammatory-diseases
#11
REVIEW
Wilhelmina Maria Cornelia Timmermans, Jan Alexander Michael van Laar, Petrus Martinus van Hagen, Menno Cornelis van Zelm
Granulomas are clusters of immune cells. These structures can be formed in reaction to infection and display signs of necrosis, such as in tuberculosis. Alternatively, in several immune disorders, such as sarcoidosis, Crohn's disease and common variable immunodeficiency, non-caseating granulomas are formed without an obvious infectious trigger. Despite advances in our understanding of the human immune system, the pathogenesis underlying these non-caseating granulomas in chronic inflammatory diseases is still poorly understood...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090319/the-role-of-liver-sinusoidal-cells-in-local-hepatic-immune-surveillance
#12
REVIEW
Dirk Wohlleber, Percy A Knolle
Although the liver's function as unique immune organ regulating immunity has received a lot of attention over the last years, the mechanisms determining hepatic immune surveillance against infected hepatocytes remain less well defined. Liver sinusoidal cells, in particular, liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs), serve as physical platform for recruitment and anchoring of blood-borne immune cells in the liver. Liver sinusoidal cells also function as portal of entry for infectious microorganisms targeting the liver such as hepatotropic viruses, bacteria or parasites...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090318/dengue-virus-antibodies-enhance-zika-virus-infection
#13
Lauren M Paul, Eric R Carlin, Meagan M Jenkins, Amanda L Tan, Carolyn M Barcellona, Cindo O Nicholson, Scott F Michael, Sharon Isern
For decades, human infections with Zika virus (ZIKV), a mosquito-transmitted flavivirus, were sporadic, associated with mild disease, and went underreported since symptoms were similar to other acute febrile diseases. Recent reports of severe disease associated with ZIKV have greatly heightened awareness. It is anticipated that ZIKV will continue to spread in the Americas and globally where competent Aedes mosquito vectors are found. Dengue virus (DENV), the most common mosquito-transmitted human flavivirus, is both well-established and the source of outbreaks in areas of recent ZIKV introduction...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090317/all-trans-retinoic-acid-enhances-cytotoxic-effect-of-t-cells-with-an-anti-cd38-chimeric-antigen-receptor-in-acute-myeloid-leukemia
#14
Tetsumi Yoshida, Keichiro Mihara, Yoshifumi Takei, Kazuyoshi Yanagihara, Takanori Kubo, Joyeeta Bhattacharyya, Chihaya Imai, Tatsuji Mino, Yoshihiro Takihara, Tatsuo Ichinohe
We reported that T cells with anti-CD38-chimeric antigen receptors (CAR) eliminated B-cell lymphoma cells expressing CD38. To employ anti-CD38-CAR against acute myeloid leukemia (AML) blasts not expressing CD38, it is necessary to induce or increase the intensity of CD38 expression. A lactate dehydrogenase (LDH)-releasing assay and flow cytometry showed that anti-CD38-CAR T cells were cytotoxic against AML lines (THP-1 and CMK) expressing high CD38 levels (>99%), in time- and number of effector-dependent manners...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090316/the-role-of-tumour-necrosis-factor-in-hepatitis-b-infection-jekyll-and-hyde
#15
REVIEW
Zina Valaydon, Marc Pellegrini, Alexander Thompson, Paul Desmond, Peter Revill, Gregor Ebert
Chronic hepatitis B (CHB) is a major health problem worldwide and is associated with significant long-term morbidity and mortality. The hepatitis B virus (HBV) is a hepatotropic virus that is capable of integrating in the host nucleus permanently resulting in lifelong infection. To date, there is no definitive cure for HBV, as our current treatments cannot eradicate the viral reservoir that has integrated in the liver. Elucidating the immunopathogenesis is key to finding a therapeutic target for HBV as the virus is not in itself cytopathic but the immune response to the virus causes the majority of the cellular injury...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28090315/chronic-mucocutaneous-candidiasis-disease-associated-with-inborn-errors-of-il-17-immunity
#16
REVIEW
Satoshi Okada, Anne Puel, Jean-Laurent Casanova, Masao Kobayashi
Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990288/infiltrating-monocytes-in-liver-injury-and-repair
#17
REVIEW
Katherine J Brempelis, Ian N Crispe
Noninfectious liver injury causes many acute and chronic liver diseases around the globe, and particularly in developed nations. Bone marrow-derived monocytes infiltrate the damaged liver tissue and are a critical component of the innate immune response that may drive injury resolution or host death in the short term or chronic inflammation, fibrosis and hepatocellular carcinoma in the long term. Monocytes often play dual roles in liver injury-both perpetuating inflammation and promoting resolution of inflammation and fibrosis...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990287/coeliac-disease-a-unique-model-for-investigating-broken-tolerance-in-autoimmunity
#18
REVIEW
Melinda Y Hardy, Jason A Tye-Din
Coeliac disease, a prevalent immune-mediated enteropathy driven by dietary gluten, provides an exceptional human model to dissect the genetic, environmental and immunologic factors operating in autoimmunity. Despite the causative antigen being an exogenous food protein, coeliac disease has many features in common with autoimmune disease including a strong HLA class II association and the presence of pathogenic CD4(+) T cells and autoantibodies. CD8(+) intraepithelial lymphocytes specifically target and destroy intestinal epithelium in response to stress signals and not a specific antigen...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990286/guanylate-binding-protein-5-is-a-marker-of-interferon-%C3%AE-induced-classically-activated-macrophages
#19
Yukio Fujiwara, Yoshiyuki Hizukuri, Kyoko Yamashiro, Naoyuki Makita, Koji Ohnishi, Motohiro Takeya, Yoshihiro Komohara, Yasuhiro Hayashi
Macrophage activation is the main immunological process occurring during the development of several diseases, and the heterogeneity of macrophage activation or differentiation has been suggested to be involved in disease progression. In the present study, we attempted to identify molecules specifically expressed on human classically activated macrophages (M1) to investigate the significance of the M1-like phenotype in human diseases. Human monocyte-derived macrophages were differentiated into M1, M2a, M2b and M2c phenotypes, and also M1(-) (the M1 phenotype differentiated with interferon-γ) to eliminate the strong effects of lipopolysaccharides (LPS) on the gene expression profile...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27990285/non-small-cell-lung-cancer-is-characterised-by-a-distinct-inflammatory-signature-in-serum-compared-with-chronic-obstructive-pulmonary-disease
#20
Hanne Astrid Eide, Ann Rita Halvorsen, Vandana Sandhu, Anne Fåne, Janna Berg, Vilde Drageset Haakensen, Elin H Kure, Odd Terje Brustugun, Cecilie Essholt Kiserud, Jon Amund Kyte, Åslaug Helland
Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD...
November 2016: Clinical & Translational Immunology
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