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Naoya Ishibashi, Tatsuaki Watanabe, Masahiko Kanehira, Yui Watanabe, Yasushi Hoshikawa, Hirotsugu Notsuda, Masafumi Noda, Akira Sakurada, Shinya Ohkouchi, Takashi Kondo, Yoshinori Okada
PURPOSE: Using a rat model of allograft lung transplantation, we investigated the effectiveness of mesenchymal stromal cells (MSCs) as prophylactic and therapeutic agents against the acute rejection of lung grafts. METHODS: Lung grafts were harvested from donor rats and transplanted orthotopically into major histocompatibility complex-mismatched rats. MSCs were administered to the recipients once (on day 0) or twice (on days 0 and 3) after transplantation. The grade of acute rejection was evaluated both macroscopically and microscopically 6 days after transplantation...
March 15, 2018: Surgery Today
Gen Murakami, Mitsuhiro Edamura, Tomonori Furukawa, Hideya Kawasaki, Isao Kosugi, Atsuo Fukuda, Toshihide Iwashita, Daiichiro Nakahara
Major histocompatibility complex class I (MHCI) is an important immune protein that is expressed in various brain regions, with its deficiency leading to extensive synaptic transmission that results in learning and memory deficits. Although MHCI is highly expressed in dopaminergic neurons, its role in these neurons has not been examined. We show that MHCI expressed in dopaminergic neurons plays a key role in suppressing reward-seeking behavior. In wild-type mice, cocaine self-administration caused persistent reduction of MHCI specifically in dopaminergic neurons, which was accompanied by enhanced glutamatergic synaptic transmission and relapse to cocaine seeking...
March 2018: Science Advances
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
Xiangpeng Chen, Baoping Xu, Jiayun Guo, Changchong Li, Shuhua An, Yunlian Zhou, Aihuan Chen, Li Deng, Zhou Fu, Yun Zhu, Chunyan Liu, Lili Xu, Wei Wang, Kunling Shen, Zhengde Xie
To identify the variations in fusion (F) protein gene of RSV in China, a molecular epidemiological study was conducted. A total of 553 RSV positive specimens were collected from 2338 pediatric patients hospitalized with community-acquired pneumonia during a multi-center study conducted during 2014-2016. A total of 252 samples (183 RSV A, 69 RSV B) were selected for F gene sequencing, and analyzed together with 142 F gene sequences downloaded from GenBank. The result showed that all the Chinese RSV A and RSV B strains could be divided respectively into three branches...
March 14, 2018: Scientific Reports
Liam V Brown, Eamonn A Gaffney, Jonathan Wagg, Mark C Coles
Tumour immunotherapy is dependent upon activation and expansion of tumour-targetting immune cells, known as cytotoxic T-lymphocytes (CTLs). Cancer vaccines developed in the past have had limited success and the mechanisms resulting in failure are not well characterized. To elucidate these mechanisms, we developed a human-parametrized, in silico , agent-based model of vaccination-driven CTL activation within a clinical short-peptide vaccination context. The simulations predict a sharp transition in the probability of CTL activation, which occurs with variation in the separation rate (or off-rate) of tumour-specific immune response-inducing peptides (cognate antigen) from the major histocompatibility class I (MHC-I) receptors of dendritic cells (DCs) originally at the vaccination site...
March 2018: Journal of the Royal Society, Interface
Linde Woudstra, Lynda J M Juffermans, Albert C van Rossum, Hans W M Niessen, Paul A J Krijnen
Infectious myocarditis is the result of an immune response to a microbial infection of the heart. The blood vessels of the heart, both the intramyocardial microvasculature and the large epicardial coronary arteries, play an important role in the pathogenesis of infectious myocarditis. First of all, in addition to cardiomyocytes, endothelial cells of the cardiac (micro)vasculature are direct targets for infection. Moreover, through the expression of adhesion molecules and antigen presenting Major Histocompatibility Complex molecules, the blood vessels assist in shaping the cellular immune response in infectious myocarditis...
March 14, 2018: Heart Failure Reviews
Megan A Schilling, Robab Katani, Sahar Memari, Meredith Cavanaugh, Joram Buza, Jessica Radzio-Basu, Fulgence N Mpenda, Melissa S Deist, Susan J Lamont, Vivek Kapur
Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust...
2018: Frontiers in Genetics
Pei Zhang, Kang Huang, Bingyi Zhang, Derek W Dunn, Dan Chen, Fan Li, Xiaoguang Qi, Songtao Guo, Baoguo Li
BACKGROUND: Maintaining variation in immune genes, such as those of the major histocompatibility complex (MHC), is important for individuals in small, isolated populations to resist pathogens and parasites. The golden snub-nosed monkey (Rhinopithecus roxellana), an endangered primate endemic to China, has experienced a rapid reduction in numbers and severe population fragmentation over recent years. For this study, we measured the DRB diversity among 122 monkeys from three populations in the Qinling Mountains, and estimated the relative importance of different agents of selection in maintaining variation of DRB genes...
March 13, 2018: BMC Evolutionary Biology
Mlatovi Dégbé, Françoise Debierre-Grockiego, Amivi Tété-Bénissan, Héloïse Débare, Kodjo Aklikokou, Isabelle Dimier-Poisson, Messanvi Gbeassor
Tectona grandis (teak) and Vernonia amygdalina (bitter leaf) are plants used in traditional medicine in West Africa. In this study, we tested ethanolic and hydro-ethanolic extracts of bark and leaves of T. grandis and ethanolic extract of leaves of V. amygdalina for their inhibitory effect on Toxoplasma gondii, a protozoan parasite responsible for toxoplasmosis. Ethanolic extract of V. amygdalina leaves had proportional contents of phenols, tannins, flavonoids, and polysaccharides. This extract presented the highest efficacy against T...
2018: Parasite: Journal de la Société Française de Parasitologie
Maryam Golshani, Melina Ghasemian, Nematollah Gheibi, Saeid Bouzari
Background: L7/L12 is a protective antigen conserved in main Brucella pathogens and is considered as potential vaccine candidate. Outer membrane protein 2b is an immunogen conserved in all Brucella pathogens. Materials and Methods: The purpose of the current study was to in silico design a L7/L12-SOmp2b fusion protein and in vitro production of the chimera. Two possible fusion forms, L7/L12-SOmp2b and SOmp2b-L7/L12, were subjected to in silico modeling and analysis...
2018: Advanced Biomedical Research
Kwok S Wun, Josephine F Reijneveld, Tan-Yun Cheng, Kristin Ladell, Adam P Uldrich, Jérôme Le Nours, Kelly L Miners, James E McLaren, Emma J Grant, Oscar L Haigh, Thomas S Watkins, Sara Suliman, Sarah Iwany, Judith Jimenez, Roger Calderon, Kattya L Tamara, Segundo R Leon, Megan B Murray, Jacob A Mayfield, John D Altman, Anthony W Purcell, John J Miles, Dale I Godfrey, Stephanie Gras, David A Price, Ildiko Van Rhijn, D Branch Moody, Jamie Rossjohn
The hallmark function of αβ T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids...
March 12, 2018: Nature Immunology
Dinler A Antunes, Didier Devaurs, Mark Moll, Gregory Lizée, Lydia E Kavraki
The class I major histocompatibility complex (MHC) is capable of binding peptides derived from intracellular proteins and displaying them at the cell surface. The recognition of these peptide-MHC (pMHC) complexes by T-cells is the cornerstone of cellular immunity, enabling the elimination of infected or tumoral cells. T-cell-based immunotherapies against cancer, which leverage this mechanism, can greatly benefit from structural analyses of pMHC complexes. Several attempts have been made to use molecular docking for such analyses, but pMHC structure remains too challenging for even state-of-the-art docking tools...
March 12, 2018: Scientific Reports
Ornella Franzese, Fiorenzo Battaini, Grazia Graziani, Lucio Tentori, Maria Luisa Barbaccia, Angelo Aquino, Mario Roselli, Maria Pia Fuggetta, Enzo Bonmassar, Francesco Torino
In recent years, immune checkpoint inhibitors (ICpI) have provided the ground to bring tumor immunity back to life thanks to their capacity to afford a real clinical benefit in terms of patient's survival. Essential to ICpI success is the presence of tumor-associated neoantigens generated by non-synonymous mutations, since a direct relationship between mutation load of malignant cells and susceptibility to ICpI has been confidently established. However, it has been also suggested that high intratumor heterogeneity (ITH) associated with subclonal neoantigens could not elicit adequate immune responses...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Florian Erhard, Anne Halenius, Cosima Zimmermann, Anne L'Hernault, Daniel J Kowalewski, Michael P Weekes, Stefan Stevanovic, Ralf Zimmer, Lars Dölken
Ribosome profiling has been used to predict thousands of short open reading frames (sORFs) in eukaryotic cells, but it suffers from substantial levels of noise. PRICE ( is a computational method that models experimental noise to enable researchers to accurately resolve overlapping sORFs and noncanonical translation initiation. We experimentally validated translation using major histocompatibility complex class I (MHC I) peptidomics and observed that sORF-derived peptides efficiently enter the MHC I presentation pathway and thus constitute a substantial fraction of the antigen repertoire...
March 12, 2018: Nature Methods
Tong Wang, Fumou Sun, Yang Wang, Jiahao Jiang, Mingzhu Pan, Minne Yuan, Hang Zhang, Xiaodian Du, Kamal Hezam, Kai Song, Min Wang, Juan Zhang
Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells...
April 2018: Journal of Immunotherapy
Jahnavi Aluri, Maya Gupta, Aparna Dalvi, Snehal Mhatre, Manasi Kulkarni, Gouri Hule, Mukesh Desai, Nitin Shah, Prasad Taur, Ramprasad Vedam, Manisha Madkaikar
Major histocompatibility complex (MHC) class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID) characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th) cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy available for treating these patients...
2018: Frontiers in Immunology
Yi-Guang Chen, Clayton E Mathews, John P Driver
For more than 35 years, the NOD mouse has been the primary animal model for studying autoimmune diabetes. During this time, striking similarities to the human disease have been uncovered. In both species, unusual polymorphisms in a major histocompatibility complex (MHC) class II molecule confer the most disease risk, disease is caused by perturbations by the same genes or different genes in the same biological pathways and that diabetes onset is preceded by the presence of circulating autoreactive T cells and autoantibodies that recognize many of the same islet antigens...
2018: Frontiers in Endocrinology
Ali Maisam Afzali, Thomas Müntefering, Heinz Wiendl, Sven G Meuth, Tobias Ruck
Histopathological analyses of muscle specimens from myositis patients indicate that skeletal muscle cells play an active role in the interaction with immune cells. Research over the last few decades has shown that skeletal muscle cells exhibit immunobiological properties that perfectly define them as non-professional antigen presenting cells. They are able to present antigens via major histocompatibility complex molecules, exhibit costimulatory molecules and secrete soluble molecules that actively shape the immune response in an either pro- or anti-inflammatory manner...
March 8, 2018: Autoimmunity Reviews
Maile K Hollinger, Valentina Giudice, Nicole A Cummings, Guillermo Rivell, Hansheng Zhang, Sachiko Kajigaya, Keyvan Keyvanfar, Jichun Chen, Xingmin Feng, Neal S Young
While PD-1 blockade has revolutionized cancer immunotherapy, immune-related adverse events (irAEs) present life-threatening complications. Recent reports of aplastic anemia (AA) as irAEs implicate PD-1/PD-L1 as important in preventing immune-mediated destruction of the hematopoietic niche. Infusion of PD-1-deficient (PD-1 KO) lymph node (LN) cells into minor-antigen mismatched mice resulted in early mortality, as well as more severe BM hypoplasia, anemia, and BM microarchitecture disruption in PD-1 KO LN-infused mice relative to mice that received B6 LN cell infusion...
March 7, 2018: Experimental Hematology
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