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https://www.readbyqxmd.com/read/29046481/reevaluation-of-immune-activation-in-the-era-of-cart-and-an-aging-hiv-infected-population
#1
Lesley R de Armas, Suresh Pallikkuth, Varghese George, Stefano Rinaldi, Rajendra Pahwa, Kristopher L Arheart, Savita Pahwa
Biological aging is associated with immune activation (IA) and declining immunity due to systemic inflammation. It is widely accepted that HIV infection causes persistent IA and premature immune senescence despite effective antiretroviral therapy and virologic suppression; however, the effects of combined HIV infection and aging are not well defined. Here, we assessed the relationship between markers of IA and inflammation during biological aging in HIV-infected and -uninfected populations. Antibody response to seasonal influenza vaccination was implemented as a measure of immune competence and relationships between IA, inflammation, and antibody responses were explored using statistical modeling appropriate for integrating high-dimensional data sets...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29045131/dapsone-and-nitroso-dapsone-activation-of-na%C3%A3-ve-t-cells-from-healthy-donors
#2
Abdulaziz Alzahrani, Monday O Ogese, Xioali Meng, James Waddington, Arun Tailor, John Farrell, James L Maggs, Catherine J Betts, B Kevin Park, Dean John Naisbitt
Dapsone (DDS) causes hypersensitivity reactions in 0.5-3.6% of patients. Although clinical diagnosis is indicative of a hypersensitivity reaction, studies have not been performed to define whether dapsone or a metabolite activates specific T-cells. Thus, the aims of this study were to explore the immunogenicity DDS and nitroso DDS (DDS-NO) using PBMC from healthy donors and splenocytes from mice and generate human T-cell clones to characterize mechanisms of T-cell activation. DDS-NO was synthesized from DDS-hydroxylamine and shown to bind to the thiol group of glutathione and human and mouse albumin through sulfonamide and N-hydroxyl sulphonamide adducts...
October 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29044495/urban-particulate-matter-stimulation-of-human-dendritic-cells-enhances-priming-of-na%C3%A3-ve-cd8-t-lymphocytes
#3
Paul E Pfeffer, Tzer R Ho, Elizabeth H Mann, Frank J Kelly, Maria Sehlstedt, Jamshid Pourazar, Rosamund E Dove, Thomas Sandstrom, Ian S Mudway, Catherine M Hawrylowicz
Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter (UPM) air pollution and exacerbations of asthma and COPD, which are both associated with viral respiratory infections. The effects of urban PM on dendritic cell (DC) stimulated CD4 T lymphocytes have been investigated previously, however little work has focused on CD8 T lymphocyte responses despite their importance in anti-viral immunity. To address this, we examined the effects of UPM on DC-stimulated naïve CD8 T cell responses...
October 16, 2017: Immunology
https://www.readbyqxmd.com/read/29042682/il-12-stimulates-ctls-to-secrete-exosomes-capable-of-activating-bystander-cd8-t-cells
#4
Lei Li, Steven M Jay, Yan Wang, Shu-Wei Wu, Zhengguo Xiao
An effective cytotoxic T lymphocyte (CTL) response against intracellular pathogens is generally accomplished by immense CTL expansion and activation, which can destroy infected cells. Vigorous immune responses can lead to activation of bystander CD8(+) T cells, but the contribution from antigen-specific CTLs is not well understood. We found that CTLs secrete extracellular vesicles following antigen stimulation. These CTL-derived vesicles contain CTL proteins and exhibit markers and size profiles consistent with exosomes...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29042482/resveratrol-stimulates-the-metabolic-reprogramming-of-human-cd4-t-cells-to-enhance-effector-function
#5
Marco Craveiro, Gaspard Cretenet, Cédric Mongellaz, Maria I Matias, Olivier Caron, Maria C Pedroso de Lima, Valérie S Zimmermann, Eric Solary, Valérie Dardalhon, Vjekoslav Dulić, Naomi Taylor
The polyphenol resveratrol activates the deacetylase Sirt1, resulting in various antioxidant, chemoprotectant, neuroprotective, cardioprotective, and anti-inflammatory properties. We found that at high concentrations of resveratrol, human CD4(+) T cells showed defective antigen receptor signaling and arrest at the G1 stage of the cell cycle, whereas at low concentrations, cells were readily activated and exhibited enhanced Sirt1 deacetylase activity. Nevertheless, low-dose resveratrol rapidly stimulated genotoxic stress in the T cells, which resulted in engagement of a DNA damage response pathway that depended on the kinase ATR [ataxia telangiectasia-mutated (ATM) and Rad3-related], but not ATM, and subsequently in premitotic cell cycle arrest...
October 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/29042319/photochemical-delivery-of-bleomycin-induces-t-cell-activation-of-importance-for-curative-effect-and-systemic-anti-tumor-immunity
#6
Ole-Jacob Norum, Ane Sofie Viset Fremstedal, Anette Weyergang, Jakub Golab, Kristian Berg
Photochemical internalization (PCI) is a technology to enhance intracellular drug delivery by light-induced translocation of endocytosed therapeutics into the cytosol. The aim of this study was to explore the efficacy of PCI-based delivery of bleomycin and the impact on systemic anti-tumor immunity. Mouse colon carcinoma cells (CT26.CL25), stably expressing the bacterial β-galactosidase, were inoculated into the legs of athymic or immuno-competent BALB/c mice strains. The mice were injected with the photosensitizer AlPcS2a and bleomycin (BLM) prior to tumor light exposure from a 670nm diode laser...
October 14, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29040430/transcriptomic-landscape-of-treatment-na%C3%A3-ve-ulcerative-colitis
#7
Hagar Taman, Christopher G Fenton, Inga V Hensel, Endre Anderssen, Jon Florholmen, Ruth H Paulssen
Background and Aims: Ulcerative colitis (UC) is a chronic inflammatory disease that effects the gastrointestinal tract and is considered one of the most prominent and common forms of inflammatory bowel disease (IBD). This study aimed to define and describe the entire transcriptomic landscape in a well-stratified, treatment-naïve UC patient population compared to control patients by using next-generation technology, RNA-Seq. Methods: Mucosal biopsies from treatment-naïve UC patients (n=14), and healthy controls (n=16) underwent RNA-Seq...
October 10, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29037907/interleukin-22-in-human-inflammatory-diseases-and-viral-infections
#8
REVIEW
Arezoo Gowhari Shabgah, Jamshid Gholizadeh Navashenaq, Omid Gohari Shabgah, Hamed Mohammadi, Amirhossein Sahebkar
Interleukin-22 (IL22) is one of the members of IL10 family. Elevated levels of this cytokine can be seen in diseases caused by T lymphocytes, such as Psoriasis, Rheumatoid arthritis, interstitial lung diseases. IL22 is produced by different cells in both innate and acquired immunities. Different types of T cells are able to produce IL22, but the major IL22-producing T-cell is the TCD4. TH22 cell is a new line of TCD4 cells, which differentiated from naive T cells in the presence of TNFα and IL6; 50% of peripheral blood IL22 is produced by these cells...
October 13, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29035947/cross-reactivity-of-hiv-vaccine-responses-and-the-microbiome
#9
Wilton B Williams, Qifeng Han, Barton F Haynes
PURPOSE OF REVIEW: A successful HIV-type 1 (HIV-1) vaccine will require immunogens that induce protective immune responses. However, recent studies suggest that the response to HIV-1 and perhaps other viruses may be altered by immune system exposure to intestinal microbiota-antigens. This review will discuss select aspects of these studies. RECENT FINDINGS: Naïve CD4 T and B cell repertoires can be imprinted by intestinal microbiota-antigens to respond to virus epitopes prior to virus infection...
October 14, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29034459/amelioration-of-autoimmunity-with-an-inhibitor-selectively-targeting-all-active-centers-of-the-immunoproteasome
#10
Michael Basler, Elmer Maurits, Gerjan de Bruin, Julia Koerner, Herman S Overkleeft, Marcus Groettrup
BACKGROUND AND PURPOSE: MECL-1 (β2i), LMP2 (β1i), and LMP7 (β5i) are the proteolytically active subunits of the immunoproteasome, a special type of proteasome mainly expressed in hematopoietic cells. Targeting LMP7 has been shown to be therapeutically effective in pre-clinical models of autoimmune diseases. In this study, a recently described inhibitor of the immunoproteasome LU-005i was investigated with respect to selectivity and biological activity. EXPERIMENTAL APPROACH: The specificity of LU-005i and other immunoproteasome selective inhibitors was characterized using fluorogenic peptide substrates...
October 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29033945/improved-efficacy-of-oral-immunotherapy-using-non-digestible-oligosaccharides-in-a-murine-cow-s-milk-allergy-model-a-potential-role-for-foxp3-regulatory-t-cells
#11
Marlotte M Vonk, Mara A P Diks, Laura Wagenaar, Joost J Smit, Raymond H H Pieters, Johan Garssen, Betty C A M van Esch, Léon M J Knippels
BACKGROUND: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. AIM: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033130/tumor-and-microenvironment-evolution-during-immunotherapy-with-nivolumab
#12
Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter J Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan
The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy...
October 11, 2017: Cell
https://www.readbyqxmd.com/read/29033080/reconstitution-of-th17-tc17-and-treg-cells-after-paediatric-haematopoietic-stem-cell-transplantation-impact-of-interleukin-7
#13
Katrine Kielsen, Lars P Ryder, David Lennox-Hvenekilde, Monika Gad, Claus H Nielsen, Carsten Heilmann, Marianne Ifversen, Anders Elm Pedersen, Klaus Müller
Successful reconstitution of T lymphocytes after allogeneic haematopoietic stem cell transplantation (HSCT) is needed to establish the graft-versus-leukaemia effect and an effective anti-microbial defense, but the ratio between functionally different T-cell subsets needs to be balanced to avoid graft-versus-host disease (GVHD). IL-7 is essential for T-cell generation in the thymus and peripheral T-cell homeostasis. High IL-7 levels have been associated with impaired T-cell reconstitution, increased risk of acute GVHD and treatment-related mortality, but the underlying cellular mechanisms behind these associations have not been investigated previously...
October 9, 2017: Immunobiology
https://www.readbyqxmd.com/read/29033003/clinicopathological-parameters-affecting-nodal-yields-in-patients-with-oral-squamous-cell-carcinoma-receiving-selective-neck-dissection
#14
Ali-Farid Safi, Martin Kauke, Andrea Grandoch, Hans-Joachim Nickenig, Uta Drebber, Joachim Zöller, Matthias Kreppel
INTRODUCTION: Nodal yield has been demonstrated as a very promising marker for the prognostic outcome of patients with oral squamous cell carcinoma. However, studies on the importance of clinicopathological factors affecting the number of resected lymph nodes are rare, especially for patients without pathologically proven cervical lymph nodes. MATERIAL AND METHODS: Retrospective chart review of 264 patients with treatment naive oral squamous cell carcinoma and histopathologically proven negative cervical lymph node status, who received selective neck dissection of levels I-III/IV...
September 10, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/29031957/exercise-training-attenuates-experimental-autoimmune-encephalomyelitis-by-peripheral-immunomodulation-rather-than-direct-neuroprotection
#15
Ofira Einstein, Nina Fainstein, Olga Touloumi, Roza Lagoudaki, Ester Hanya, Nikolaos Grigoriadis, Abram Katz, Tamir Ben-Hur
BACKGROUND: Conflicting results exist on the effects of exercise training (ET) on Experimental Autoimmune Encephalomyelitis (EAE), nor is it known how exercise impacts on disease progression. OBJECTIVE: We examined whether ET ameliorates the development of EAE by modulating the systemic immune system or exerting direct neuroprotective effects on the CNS. METHODS: Healthy mice were subjected to 6weeks of motorized treadmill running. The Proteolipid protein (PLP)-induced transfer EAE model in mice was utilized...
October 11, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29031634/fecal-bacteria-from-treatment-naive-crohn-s-disease-patients-can-skew-helper-t-cell-responses
#16
Fei Ma, Yi Zhang, Junjie Xing, Xiaoling Song, Ling Huang, Hao Weng, Xiangsong Wu, Emma Walker, Zhongchuan Wang
Many studies have demonstrated that the inflamed mucosa of Crohn's disease (CD) patients presented a disturbed gut commensal community, and the shift in microbial composition and species variety is associated with disease severity. To establish a link between changes in the intestinal bacterial composition and the alteration of inflammation, we obtained fecal bacteria from CD patients and non-CD controls. The bacteria were then used to stimulate the peripheral blood mononuclear cells (PBMCs) from one non-CD individual...
October 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29030820/investigating-cellular-quiescence-of-t-lymphocytes-and-antigen-induced-exit-from-quiescence
#17
Kai Yang, Hongbo Chi
Naïve T cells are in a quiescent state under homeostasis but respond to antigen stimulation by exiting from quiescence and entering the cell cycle. Appropriate regulation of quiescence is crucial for maintaining T cell homeostasis at steady state and initiating proper T cell responses to antigen stimulation. Emerging evidence indicates that signaling by mechanistic target of rapamycin (mTOR) plays a central role in the control of T cell quiescence and antigen-induced exit from quiescence through coordinating immune signals, cellular metabolic programs, and cell cycle machinery...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29030115/store-operated-ca-2-entry-controls-clonal-expansion-of-t-cells-through-metabolic-reprogramming
#18
Martin Vaeth, Mate Maus, Stefan Klein-Hessling, Elizaveta Freinkman, Jun Yang, Miriam Eckstein, Scott Cameron, Stuart E Turvey, Edgar Serfling, Friederike Berberich-Siebelt, Richard Possemato, Stefan Feske
Store-operated Ca(2+) entry (SOCE) is the main Ca(2+) influx pathway in lymphocytes and is essential for T cell function and adaptive immunity. SOCE is mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels that are activated by stromal interaction molecule (STIM) 1 and STIM2. SOCE regulates many Ca(2+)-dependent signaling molecules, including calcineurin, and inhibition of SOCE or calcineurin impairs antigen-dependent T cell proliferation. We here report that SOCE and calcineurin regulate cell cycle entry of quiescent T cells by controlling glycolysis and oxidative phosphorylation...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29024417/human-cd8-emra-t-cells-display-a-senescence-associated-secretory-phenotype-regulated-by-p38-mapk
#19
Lauren A Callender, Elizabeth C Carroll, Robert W J Beal, Emma S Chambers, Sussan Nourshargh, Arne N Akbar, Sian M Henson
Cellular senescence is accompanied by a senescence-associated secretory phenotype (SASP). We show here that primary human senescent CD8(+) T cells also display a SASP comprising chemokines, cytokines and extracellular matrix remodelling proteases that are unique to this subset and contribute to age-associated inflammation. We found the CD8(+) CD45RA(+) CD27(-) EMRA subset to be the most heterogeneous, with a population aligning with the naïve T cells and another with a closer association to the effector memory subset...
October 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/29023774/transmission-of-a-common-intestinal-neoplasm-in-zebrafish-by-cohabitation
#20
A R Burns, V Watral, S Sichel, S Spagnoli, A V Banse, E Mittge, T J Sharpton, K Guillemin, M L Kent
Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities. These tumours are most often seen in older fish and are classified as small cell carcinomas or adenocarcinomas. Affected fish populations always contain subpopulations with preneoplastic lesions, characterized by epithelial hyperplasia or inflammation. Previous observations indicated that these tumours are unlikely caused by diet, water quality or genetic background, suggesting an infectious aetiology. We performed five transmission experiments by exposure of naïve fish to affected donor fish by cohabitation or exposure to tank effluent water...
October 11, 2017: Journal of Fish Diseases
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