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https://www.readbyqxmd.com/read/29220865/silver-nano-particles-ameliorate-learning-and-spatial-memory-of-male-wistar-rats-by-prevention-of-amyloid-fibril-induced-neurotoxicity
#1
H Ramshini, A-S Moghaddasi, L-S Aldaghi, N Mollania, A Ebrahim-Habibi
Alzheimer's disease (AD) is a chronic degenerative disease characterized by the presence of amyloid plaques and neurofibrillary tangles (NFTs), which results into memory and learning impairments. In the present study, we showed that the aggregates formed by a protein that has no link with Alzheimer's disease, namely the hen egg white lysozyme (HEWL), were cytotoxic and decreased spatial learning and memory in rats. The effect of Ag-nano particles (Ag-NPs) was investigated on disruption of amyloid aggregation and preservation of cognitive behavior of rats...
December 8, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29218403/the-storage-and-recall-of-memories-in-the-hippocampo-cortical-system
#2
REVIEW
Edmund T Rolls
A quantitative computational theory of the operation of the hippocampus as an episodic memory system is described. The CA3 system operates as a single attractor or autoassociation network (1) to enable rapid one-trial associations between any spatial location (place in rodents or spatial view in primates) and an object or reward and (2) to provide for completion of the whole memory during recall from any part. The theory is extended to associations between time and object or reward to implement temporal order memory, which is also important in episodic memory...
December 7, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29218113/age-associated-alteration-in-th17-cell-response-is-related-to-endothelial-cell-senescence-and-atherosclerotic-cerebral-infarction
#3
Qing Li, Shaowei Ding, Yuan Min Wang, Xiaoling Xu, Zuojun Shen, Rui Fu, Mengdie Liu, Chaojie Hu, Cuiping Zhang, Qi Cao, Yiping Wang
T-helper 17 (Th17) cells produce Interleukin-17 (IL-17) that plays an important role in host-defense. However, little is known whether aging affects the functions of human Th17 cells. In this study, we examine age-associated alteration in Th17-cell response; correlation between Th17-cells and endothelial cell senescence; and the occurrence of acute cerebral infarction (ACI). First, we examined Th17-frequency, phenotyping, key transcription factors, and relevant cytokines in healthy elderly, middle-aged and young-people along with elderly-patients with ACI...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29217528/t-cells-expressing-checkpoint-receptor-tigit-are-enriched-in-follicular-lymphoma-tumors-and-characterized-by-reversible-suppression-of-t-cell-receptor-signaling
#4
Sarah E Josefsson, Kanutte Huse, Arne Kolstad, Klaus Beiske, Daniela Pende, Chloé B Steen, Else Marit Inderberg, Ole Christian Lingjærde, Bjørn Østenstad, Erlend B Smeland, Ronald Levy, Jonathan M Irish, June H Myklebust
PURPOSE: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing co-inhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets. EXPERIMENTAL DESIGN: Surface expression of 9 co-inhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry...
December 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29217460/tissue-specific-cellular-immune-responses-to-malaria-pre-erythrocytic-stages
#5
REVIEW
Olivier Silvie, Rogerio Amino, Julius Clemence Hafalla
Complete and long-lasting protective immunity against malaria can be achieved through vaccination with invasive live attenuated Plasmodium sporozoites, the motile stage inoculated in the host skin during a mosquito bite. Protective immunity relies primarily on effector CD8+ T cells targeting the parasite in the liver. Understanding the tissue-specific features of the immune response is emerging as a vital requirement for understanding protective immunity. The small parasite inoculum, the scarcity of infected cells and the tolerogenic properties of the liver represent hurdles for the establishment of protective immunity in endemic areas...
December 4, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29217299/high-pd-l1-cd86-mfi-ratio-and-il-10-secretion-characterize-human-regulatory-dendritic-cells-generated-for-clinical-testing-in-organ-transplantation
#6
Alan F Zahorchak, Camila Macedo, David E Hamm, Lisa H Butterfield, Diana M Metes, Angus W Thomson
Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression...
September 14, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#7
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29214034/identification-of-biomarkers-of-response-to-abatacept-in-patients-with-sle-using-deconvolution-of-whole-blood-transcriptomic-data-from-a-phase-iib-clinical-trial
#8
Somnath Bandyopadhyay, Sean E Connolly, Omar Jabado, June Ye, Sheila Kelly, Michael A Maldonado, Rene Westhovens, Peter Nash, Joan T Merrill, Robert M Townsend
Objective: To characterise patients with active SLE based on pretreatment gene expression-defined peripheral immune cell patterns and identify clusters enriched for potential responders to abatacept treatment. Methods: This post hoc analysis used baseline peripheral whole blood transcriptomic data from patients in a phase IIb trial of intravenous abatacept (~10 mg/kg/month). Cell-specific genes were used with a published deconvolution algorithm to identify immune cell proportions in patient samples, and unsupervised consensus clustering was generated...
2017: Lupus Science & Medicine
https://www.readbyqxmd.com/read/29213267/revealing-the-complexity-in-cd8-t-cell-responses-to-infection-in-inbred-c57b-6-versus-outbred-swiss-mice
#9
Matthew D Martin, Derek B Danahy, Stacey M Hartwig, John T Harty, Vladimir P Badovinac
Recent work has suggested that current mouse models may underrepresent the complexity of human immune responses. While most mouse immunology studies utilize inbred mouse strains, it is unclear if conclusions drawn from inbred mice can be extended to all mouse strains or generalized to humans. We recently described a "surrogate activation marker" approach that could be used to track polyclonal CD8 T cell responses in inbred and outbred mice and noted substantial discord in the magnitude and kinetics of CD8 T cell responses in individual outbred mice following infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29212954/inhibition-of-akt-signaling-uncouples-t-cell-differentiation-from-expansion-for-receptor-engineered-adoptive-immunotherapy
#10
Christopher A Klebanoff, Joseph G Crompton, Anthony J Leonardi, Tori N Yamamoto, Smita S Chandran, Robert L Eil, Madhusudhanan Sukumar, Suman K Vodnala, Jinhui Hu, Yun Ji, David Clever, Mary A Black, Devikala Gurusamy, Michael J Kruhlak, Ping Jin, David F Stroncek, Luca Gattinoni, Steven A Feldman, Nicholas P Restifo
Adoptive immunotherapies using T cells genetically redirected with a chimeric antigen receptor (CAR) or T cell receptor (TCR) are entering mainstream clinical practice. Despite encouraging results, some patients do not respond to current therapies. In part, this phenomenon has been associated with infusion of reduced numbers of early memory T cells. Herein, we report that AKT signaling inhibition is compatible with CAR and TCR retroviral transduction of human T cells while promoting a CD62L-expressing central memory phenotype...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29212909/pd-l1-prevents-the-development-of-autoimmune-heart-disease-in-graft-versus-host-disease
#11
Kathryn W Juchem, Faruk Sacirbegovic, Cuiling Zhang, Arlene H Sharpe, Kerry Russell, Jennifer M McNiff, Anthony J Demetris, Mark J Shlomchik, Warren D Shlomchik
Effector memory T cells (TEM) are less capable of inducing graft-versus-host disease (GVHD) compared with naive T cells (TN). Previously, in the TS1 TCR transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found that cell-intrinsic properties of TS1 TEM reduced their GVHD potency relative to TS1 TN Posttransplant, TS1 TEM progeny expressed higher levels of PD-1 than did TS1 TN progeny, leading us to test the hypothesis that TEM induce less GVHD because of increased sensitivity to PD-ligands...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29211912/intestinal-t-cell-profiling-in-inflammatory-bowel-disease-linking-t-cell-subsets-to-disease-activity-and-disease-course
#12
Carolijn Smids, Carmen S Horjus Talabur Horje, Julia Drylewicz, Britt Roosenboom, Marcel J M Groenen, Elly van Koolwijk, Ellen G van Lochem, Peter J Wahab
Introduction: A dysregulated intestinal T-cell response is presumed in patients with Inflammatory Bowel Disease (IBD). In this longitudinal study, we investigated the changes in intestinal T lymphocyte subsets in IBD at first presentation and over time during endoscopic active or inactive disease and relate them to disease activity and outcome. Material & method: We included 129 newly diagnosed patients (87 Crohn´s Disease (CD), 42 ulcerative colitis (UC)) and 19 healthy controls (HC)...
December 4, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29211713/runx3-programs-cd8-t-cell-residency-in-non-lymphoid-tissues-and-tumours
#13
J Justin Milner, Clara Toma, Bingfei Yu, Kai Zhang, Kyla Omilusik, Anthony T Phan, Dapeng Wang, Adam J Getzler, Toan Nguyen, Shane Crotty, Wei Wang, Matthew E Pipkin, Ananda W Goldrath
Tissue-resident memory CD8+ T (TRM) cells are found at common sites of pathogen exposure, where they elicit rapid and robust protective immune responses. However, the molecular signals that control TRM cell differentiation and homeostasis are not fully understood. Here we show that mouse TRM precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, we identify the transcription factor Runx3 as a key regulator of TRM cell differentiation and homeostasis...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29209572/trial-watch-immunostimulatory-monoclonal-antibodies-for-oncological-indications
#14
REVIEW
Mariona Cabo, Rienk Offringa, Laurence Zitvogel, Guido Kroemer, Aura Muntasell, Lorenzo Galluzzi
The goal of cancer immunotherapy is to establish new or boost pre-existing anticancer immune responses that eradicate malignant cells while generating immunological memory to prevent disease relapse. Over the past few years, immunomodulatory monoclonal antibodies (mAbs) that block co-inhibitory receptors on immune effectors cells - such as cytotoxic T lymphocyte-associated protein 4 (CTLA4), programmed cell death 1 (PDCD1, best known as PD-1) - or their ligands - such as CD274 (best known as PD-L1) - have proven very successful in this sense...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29209568/phenotype-and-tissue-distribution-of-cd28h-immune-cell-subsets
#15
Joel Crespo, Linda Vatan, Tomasz Maj, Rebecca Liu, Ilona Kryczek, Weiping Zou
CD28H is a newly discovered co-receptor of the human B7 family. CD28H interacts with its ligand B7-H5 and regulates T cell response. Here we showed that CD28H was not expressed on granulocytes, monocytes, myeloid dendritic cells (MDCs), and B cells, but constitutively expressed with moderate levels on memory T cells and with high levels on naïve T cells, innate lymphoid cells (ILCs), natural killer (NK) cells, and plasmacytoid dendritic cells (PDCs) in human peripheral blood. Similar CD28H+ cell profile existed in secondary lymphoid organs and pathological tissues including multiple types of cancers...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29209565/tumor-targeted-costimulation-with-antibody-fusion-proteins-improves-bispecific-antibody-mediated-immune-response-in-presence-of-immunosuppressive-factors
#16
Sabrina Sapski, Nadine Beha, Roland Kontermann, Dafne Müller
Therapeutic strategies aiming for the induction of an effective immune response at the tumor site can be severely hampered by the encounter of an immunosuppressive microenvironment. We investigated here the potential of concerted costimulation by tumor-directed antibody-fusion proteins with B7.1, 4-1BBL and OX40L to enforce bispecific antibody-induced T cell stimulation in presence of recognized immunosuppressive factors including IL-10, TGF-β, indoleamine 2,3-dioxygenase (IDO), PD-L1 and regulatory T cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29208744/severity-of-acute-infectious-mononucleosis-correlates-with-cross-reactive-influenza-cd8-t-cell-receptor-repertoires
#17
Nuray Aslan, Levi B Watkin, Anna Gil, Rabinarayan Mishra, Fransenio G Clark, Raymond M Welsh, Dario Ghersi, Katherine Luzuriaga, Liisa K Selin
Fifty years after the discovery of Epstein-Barr virus (EBV), it remains unclear how primary infection with this virus leads to massive CD8 T-cell expansion and acute infectious mononucleosis (AIM) in young adults. AIM can vary greatly in severity, from a mild transient influenza-like illness to a prolonged severe syndrome. We questioned whether expansion of a unique HLA-A2.01-restricted, cross-reactive CD8 T-cell response between influenza virus A-M158 (IAV-M1) and EBV BMLF1280 (EBV-BM) could modulate the immune response to EBV and play a role in determining the severity of AIM in 32 college students...
December 5, 2017: MBio
https://www.readbyqxmd.com/read/29207606/combination-therapy-with-an-ox40l-fusion-protein-and-a-vaccine-targeting-the-transcription-factor-twist-inhibits-metastasis-in-a-murine-model-of-breast-cancer
#18
Anthony S Malamas, Scott A Hammond, Jeffrey Schlom, James W Hodge
OX40 is a costimulatory receptor that potentiates proliferation, survival, memory formation, and effector function of CD4+ and CD8+ T-cells, while overcoming the suppressive activity of regulatory T-cells (Tregs). Here, we explored the combination of an OX40L fusion protein (OX40L-FP) with a poxvirus-based cancer vaccine (MVA-Twist-TRICOM) to inhibit tumor metastasis in the 4T1 murine breast cancer model. Contrary to the single agent treatments, the combination therapy significantly decreased the number of metastatic colonies per lung and prolonged survival...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29206240/influence-of-an-immunodominant-herpes-simplex-virus-type-1-cd8-t-cell-epitope-on-the-target-hierarchy-and-function-of-subdominant-cd8-t-cells
#19
Benjamin R Treat, Sarah M Bidula, Srividya Ramachandran, Anthony J St Leger, Robert L Hendricks, Paul R Kinchington
Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal ganglia (TG) is associated with a persistent immune infiltrate that includes effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6 mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+ T cells (gB-CD8s) recognize a single epitope on glycoprotein B (gB498-505), while the remainder (non-gB-CD8s) recognize, in varying proportions, 19 subdominant epitopes on 12 viral proteins. The gB-CD8s remain functional in TG throughout latency, while non-gB-CD8s exhibit varying degrees of functional compromise...
December 4, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29204145/molecular-signatures-of-immunity-and-immunogenicity-in-infection-and-vaccination
#20
REVIEW
Mariëlle C Haks, Barbara Bottazzi, Valentina Cecchinato, Corinne De Gregorio, Giuseppe Del Giudice, Stefan H E Kaufmann, Antonio Lanzavecchia, David J M Lewis, Jeroen Maertzdorf, Alberto Mantovani, Federica Sallusto, Marina Sironi, Mariagrazia Uguccioni, Tom H M Ottenhoff
Vaccinology aims to understand what factors drive vaccine-induced immunity and protection. For many vaccines, however, the mechanisms underlying immunity and protection remain incompletely characterized at best, and except for neutralizing antibodies induced by viral vaccines, few correlates of protection exist. Recent omics and systems biology big data platforms have yielded valuable insights in these areas, particularly for viral vaccines, but in the case of more complex vaccines against bacterial infectious diseases, understanding is fragmented and limited...
2017: Frontiers in Immunology
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