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https://www.readbyqxmd.com/read/28548945/soluble-antigens-from-the-neurotropic-pathogen-angiostrongylus-cantonensis-directly-induce-thymus-atrophy-in-a-mouse-model
#1
Zhen Liu, Dong-Ming Su, Zi-Long Yu, Feng Wu, Rui-Feng Liu, Shi-Qi Luo, Zhi-Yue Lv, Xin Zeng, Xi Sun, Zhong-Dao Wu
The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infectedmouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents...
May 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28546760/analysis-of-immune-status-after-iodine-125-permanent-brachytherapy-in-prostate-cancer
#2
E Du, Lin Wang, Chang-Ying Li, Chang-Wen Zhang, Yan-Chun Qu, Ran-Lu Liu, Yong Xu, Kuo Yang, Zhi-Hong Zhang
BACKGROUND: Permanent prostate brachytherapy (PPB) is an effective treatment choice for low and intermediate risk prostate cancer (PCa). However, the impact of PPB on tumor immune status is still poorly understood. This study aimed to assess the immune status in PCa patients before and at different time points after PPB (1, 3, 6, and 12 months). METHODS: Blood was collected from 32 patients with low and intermediate risk PCa and 12 healthy volunteers. The frequency of immunocompetent cells was identified by flow cytometry...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28546503/frontline-science-functionally-impaired-geriatric-car-t-cells-rescued-by-increased-%C3%AE-5%C3%AE-1-integrin-expression
#3
Prajna Guha, Marissa Cunetta, Ponnandai Somasundar, N Joseph Espat, Richard P Junghans, Steven C Katz
Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28544524/increase-of-cells-expressing-pd-1-and-pd-l1-and-enhancement-of-ifn-%C3%AE-production-via-pd-1-pd-l1-blockade-in-bovine-mycoplasmosis
#4
Shinya Goto, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Naoya Maekawa, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
INTRODUCTION: Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis...
May 24, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28543181/loss-of-l-selectin-guided-cd8-but-not-cd4-cells-protects-against-ischemia-reperfusion-injury-in-a-steatotic-liver
#5
Vasantha L Kolachala, Sirish Palle, Ming Shen, Alayna Feng, Dmitry Shayakhmetov, Nitika A Gupta
BACKGROUND & AIMS: Steatotic liver responds with increased hepatocellular injury when exposed to an ischemic-reperfusion insult. Increasing evidence supports the role of immune cells as key mediators of this injury in a normal (lean) state, but data about their role in a steatotic liver are practically non-existent. The objective of the current study was to delineate contribution of specific phenotypes of T cells and adhesion molecules in exacerbated cell death in steatotic liver injury...
May 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28543170/specific-activation-of-cd4-cd8-double-negative-t-cells-by-t-cruzi-derived-glycolipids-induces-a-pro-inflammatory-profile-associated-with-cardiomyopathy-in-chagas-patients
#6
Lívia Silva Araújo Passos, Luísa Mourão Dias Magalhães, Rodrigo Pedro Soares, Alexandre F Marques, Maria do Carmo Pereira Nunes, Kenneth J Gollob, Walderez Ornelas Dutra
Cardiomyopathy is the most severe outcome of Chagas disease, causing over 12,000 deaths/year. Immune cells participate in cardiomyopathy development either by direct tissue destruction, or by driving inflammation. We have shown that CD4-CD8- (double negative - DN) T cells are major sources of inflammatory and anti-inflammatory cytokines, associated with the cardiac (CARD) and indeterminate (IND) forms of Chagas disease, respectively. Here, we sought to identify Trypanosoma cruzi derived components that lead to activation of DN T cells in Chagas patients...
May 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28542613/suppression-of-il-12p70-formation-by-il-2-or-following-macrophage-depletion-causes-t-cell-autoreactivity-leading-to-cns-demyelination-in-hsv-1-infected-mice
#7
Dhong Hyun Lee, Mandana Zandian, Jane Kuo, Kevin R Mott, Shuang Chen, Moshe Arditi, Homayon Ghiasi
We have established two mouse models of central nervous system (CNS) demyelination that differ from most other available models of multiple sclerosis (MS) in that they represent a mixture of viral and immune triggers. In the first model, ocular infection of different strains of mice with a recombinant HSV-1 that expresses murine IL-2 constitutively (HSV-IL-2) causes CNS demyelination. In the second model, depletion of macrophages causes CNS demyelination in mice that are ocularly infected with wild-type (WT) HSV-1...
May 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542586/antigen-delivery-to-dendritic-cells-shapes-human-cd4-and-cd8-t-cell-memory-responses-to-staphylococcus-aureus
#8
Julia Uebele, Christoph Stein, Minh-Thu Nguyen, Anja Schneider, Franziska Kleinert, Olga Tichá, Gabriele Bierbaum, Friedrich Götz, Isabelle Bekeredjian-Ding
Intracellular persistence of Staphylococcus aureus favors bacterial spread and chronic infections. Here, we provide evidence for the existence of human CD4+ and CD8+ T cell memory against staphylococcal antigens. Notably, the latter could provide a missing link in our understanding of immune control of intracellular S. aureus. The analyses showed that pulsing of monocyte-derived dendritic cells (MoDC) with native staphylococcal protein antigens induced release of Th2-associated cytokines and mediators linked to T regulatory cell development (G-CSF, IL-2 and IL-10) from both CD4+ and CD8+ T cells, thus revealing a state of tolerance predominantly arising from preformed memory T cells...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28542574/combination-therapy-of-cancer-with-cancer-vaccine-and-immune-checkpoint-inhibitors-a-mathematical-model
#9
Xiulan Lai, Avner Friedman
In this paper we consider a combination therapy of cancer. One drug is a vaccine which activates dendritic cells so that they induce more T cells to infiltrate the tumor. The other drug is a checkpoint inhibitor, which enables the T cells to remain active against the cancer cells. The two drugs are positively correlated in the sense that an increase in the amount of each drug results in a reduction in the tumor volume. We consider the question whether a treatment with combination of the two drugs at certain levels is preferable to a treatment by one of the drugs alone at 'roughly' twice the dosage level; if that is the case, then we say that there is a positive 'synergy' for this combination of dosages...
2017: PloS One
https://www.readbyqxmd.com/read/28539651/an-orthologous-non-mhc-locus-in-rats-and-mice-is-linked-to-cd4-and-cd8-t-cell-proportion
#10
D Franckaert, R Collin, J Dooley, R H Wallis, P Poussier, A Liston, E E Hillhouse, S Lesage
CD4(+) and CD8(+) T cells have a central role in the immune system due to their ability to protect against infection and cancer development without targeting self. Consequently, changes in CD4(+) and CD8(+) T-cell homeostasis can be indicative of an array of serious illnesses, ranging from viral infections to autoimmune diseases. In addition to environmental influences, there is evidence for a genetic component regulating the proportion of CD4(+) and CD8(+) T cells in lymphoid organs. Indeed, identifying the genetic determinants defining the frequency of the T-cell subsets is critical as it may reveal a targetable genetic pathway to modulate CD4(+) and CD8(+) T-cell numbers, which could be of clinical relevance for multiple disease settings...
May 25, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28539628/low-level-of-lck-kinase-in-th2-cells-limits-expression-of-cd4-co-receptor-and-s73-phosphorylation-of-transcription-factor-c-jun
#11
Yury V Shebzukhov, Silke Stanislawiak, Taisiya R Bezhaeva, Sergei A Nedospasov, Dmitry V Kuprash
The Src-family tyrosine kinase Lck is an enzyme associated with the CD4 and CD8 co-receptors and promoting signaling through the T cell receptor (TCR) complex. The levels of Lck expression and activity change during the development and differentiation of T cells. Here we show that Lck expression is higher in Th1 cells as compared to Th2 cells. Ectopic overexpression of Lck in Th2 cells results in increased expression of CD4 co-receptor and enhanced S73 phosphorylation of transcription factor c-Jun. Our findings indicate that TCR-mediated signaling in Th2 cells may be directly attenuated by Lck protein expression level...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539588/cooperation-of-oncolytic-herpes-virotherapy-and-pd-1-blockade-in-murine-rhabdomyosarcoma-models
#12
Chun-Yu Chen, Pin-Yi Wang, Brian Hutzen, Les Sprague, Hayley M Swain, Julia K Love, Joseph R Stanek, Louis Boon, Joe Conner, Timothy P Cripe
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion of antitumor T cell responses. Solid tumors limit the effectiveness of immunotherapeutics in diverse ways such as secretion of immunosuppressive cytokines and expression of immune inhibitory ligands to inhibit antitumor T cell function. Blocking programmed cell death protein (PD)-1 signaling, which mediates T cell suppression via engagement of its inhibitory ligands, PD-L1 or PD-L2, is of particular interest due to recent successes in many types of cancer...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28539448/virological-control-by-the-cd4-binding-site-antibody-n6-in-shiv-infected-rhesus-monkeys
#13
Boris Julg, Amarendra Pegu, Peter Abbink, Jinyan Liu, Amanda Brinkman, Katherine Molloy, Shanell Mojta, Abishek Chandrashekar, Katherine Callow, Keyun Wang, Xuejun Chen, Stephen D Schmidt, Jinghe Huang, Richard A Koup, Michael S Seaman, Brandon F Keele, John R Mascola, Mark Connors, Dan H Barouch
Passive immunotherapies against HIV-1 will most likely require broadly neutralizing antibodies (bnAb) with maximum breadth and potency to assure therapeutic efficacy. Recently, the novel CD4 binding site antibody N6 demonstrated extraordinary neutralization breadth and potency against large panels of cross clade pseudoviruses. We evaluated the in-vivo antiviral activity of N6-LS, alone or in combination with the established V3-glycan antibody PGT121, in chronically SHIV-SF162P3 infected macaques. A single dose of N6-LS suppressed plasma viral loads in 4 out of 5 animals at day 7 (mean 1...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28537254/large-scale-meta-analysis-characterizes-genetic-architecture-for-common-psoriasis-associated-variants
#14
Lam C Tsoi, Philip E Stuart, Chao Tian, Johann E Gudjonsson, Sayantan Das, Matthew Zawistowski, Eva Ellinghaus, Jonathan N Barker, Vinod Chandran, Nick Dand, Kristina Callis Duffin, Charlotta Enerbäck, Tõnu Esko, Andre Franke, Dafna D Gladman, Per Hoffmann, Külli Kingo, Sulev Kõks, Gerald G Krueger, Henry W Lim, Andres Metspalu, Ulrich Mrowietz, Sören Mucha, Proton Rahman, Andre Reis, Trilokraj Tejasvi, Richard Trembath, John J Voorhees, Stephan Weidinger, Michael Weichenthal, Xiaoquan Wen, Nicholas Eriksson, Hyun M Kang, David A Hinds, Rajan P Nair, Gonçalo R Abecasis, James T Elder
Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including TH0, TH1 and TH17)...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28537249/airway-t-cells-protect-against-rsv-infection-in-the-absence-of-antibody
#15
E Kinnear, L Lambert, J U McDonald, H M Cheeseman, L J Caproni, J S Tregoning
Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8(+) Trm cells (CD103(+)/CD69(+)) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice...
May 24, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28537062/evaluation-of-the-immunogenicity-and-impact-on-the-latent-hiv-1-reservoir-of-a-conserved-region-vaccine-mva-hivconsv-in-antiretroviral-therapy-treated-subjects
#16
REVIEW
Gemma Hancock, Sara Morón-López, Jakub Kopycinski, Maria C Puertas, Eleni Giannoulatou, Annie Rose, Maria Salgado, Emma-Jo Hayton, Alison Crook, Catharine Morgan, Brian Angus, Fabian Chen, Hongbing Yang, Javier Martinez-Picado, Tomas Hanke, Lucy Dorrell
INTRODUCTION: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA). METHODS: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA.HIVconsv (5.5 × 10(7) plaque-forming units, pfu, n = 8; 2...
May 19, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28537058/unusual-suspects-in-the-development-of-obesity-induced-inflammation-and-insulin-resistance-nk-cells-inkt-cells-and-ilcs
#17
REVIEW
Beatriz Dal Santo Francisco Bonamichi, Jongsoon Lee
The notion that obesity-induced inflammation mediates the development of insulin resistance in animal models and humans has been gaining strong support. It has also been shown that immune cells in local tissues, in particular in visceral adipose tissue, play a major role in the regulation of obesity-induced inflammation. Specifically, obesity increases the numbers and activation of proinflammatory immune cells, including M1 macrophages, neutrophils, Th1 CD4 T cells, and CD8 T cells, while simultaneously suppressing anti-inflammatory cells such as M2 macrophages, CD4 regulatory T cells, regulatory B cells, and eosinophils...
May 22, 2017: Diabetes & Metabolism Journal
https://www.readbyqxmd.com/read/28536921/progressive-multifocal-leukoencephalopathy-in-patients-treated-with-fumaric-acid-esters-a-review-of-19-cases
#18
Robbert-Jan Gieselbach, Annemarie H Muller-Hansma, Martijn T Wijburg, Marjolein S de Bruin-Weller, Bob W van Oosten, Dennis J Nieuwkamp, Frank E Coenjaerts, Mike P Wattjes, Jean-Luc Murk
Progressive multifocal leukoencephalopathy (PML) is a rare and potentially fatal condition caused by a brain infection with JC polyomavirus (JCV). PML develops almost exclusively in immunocompromised patients and has recently been associated with use of fumaric acid esters (FAEs), or fumarates. We reviewed the literature and the Dutch and European pharmacovigilance databases in order to identify all available FAE-associated PML cases and distinguish possible common features among these patients. A total of 19 PML cases associated with FAE use were identified...
May 23, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28536278/immune-checkpoint-blockade-immunogenic-chemotherapy-or-ifn-%C3%AE-blockade-boost-the-local-and-abscopal-effects-of-oncolytic-virotherapy
#19
Laetitia Fend, Takahiro Yamazaki, Christelle Remy, Catherine Fahrner, Murielle Gantzer, Virginie Nourtier, Xavier Préville, Eric Quéméneur, Oliver Kepp, Julien Adam, Aurélien Marabelle, Jonathan M Pitt, Guido Kroemer, Laurence Zitvogel
Athough the clinical efficacy of oncolytic viruses has been demonstrated for local treatment, the ability to induce immune-mediated regression of distant metastases is still poorly documented. We report here that the engineered oncolytic vaccinia virus VVWR-TK(-)RR(-)-Fcu1 can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8(+) T cells, and immune cell infiltrate in the tumor could be reprogrammed towards a higher ratio of effector T cells to regulatory CD4(+) T cells...
May 23, 2017: Cancer Research
https://www.readbyqxmd.com/read/28535968/abnormal-distribution-of-distinct-lymphocyte-subsets-in-children-with-wiskott-aldrich-syndrome
#20
Lina Zhou, Wenyan Li, Xuan Zhang, Dawei Liu, Yuan Ding, Rongxin Dai, Xiaodong Zhao
Wiskott-Aldrich syndrome (WAS) is a severe and rare primary immunodeficiency. Several studies show that WAS protein (WASp) plays a key role in the function of certain lymphocyte subsets. So far, no study has described distinct immunophenotypic abnormalities associated with WAS; thus the prognostic significance of any such abnormalities is unclear. This study examined many differences in the percentage/absolute numbers of distinct lymphocyte subsets in 20 WAS patients and 20 age/sex-matched healthy controls, and analyzed the association between these abnormalities and clinical disease scores...
May 20, 2017: Human Immunology
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