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https://www.readbyqxmd.com/read/28331616/ex-vivo-akt-inhibition-promotes-the-generation-of-potent-cd19car-t-cells-for-adoptive-immunotherapy
#1
Ryan Urak, Miriam Walter, Laura Lim, ChingLam W Wong, Lihua E Budde, Sandra Thomas, Stephen J Forman, Xiuli Wang
BACKGROUND: Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation. We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28261215/tnf-blockade-maintains-an-il-10-phenotype-in-human-effector-cd4-and-cd8-t-cells
#2
Ceri A Roberts, Lucy E Durham, Veerle Fleskens, Hayley G Evans, Leonie S Taams
CD4(+) and CD8(+) effector T cell subpopulations can display regulatory potential characterized by expression of the prototypically anti-inflammatory cytokine IL-10. However, the underlying cellular mechanisms that regulate expression of IL-10 in different T cell subpopulations are not yet fully elucidated. We recently showed that TNF inhibitors (TNFi) promote IL-10 expression in human CD4(+) T cells, including IL-17(+) CD4(+) T cells. Here, we further characterized the regulation of IL-10 expression via blockade of TNF signaling or other cytokine/co-stimulatory pathways, in human T cell subpopulations...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28260094/immunosuppressive-macrophages-induced-by-ido1-promote-the-growth-of-endometrial-stromal-cells-in-endometriosis
#3
Jie Mei, Kai-Kai Chang, Hai-Xiang Sun
It was previously demonstrated that anomalous expression of indoleamine 2,3-dioxygenase-1 (IDO1) in endometrial stromal cells (ESCs) stimulated an inflammatory response that subsequently initiated the activation of immunosuppressive macrophages in endometriosis. The aim of the present study was to clarify the effect of IDO1‑induced macrophages on the growth of ESCs in endometriosis. Normal ESCs, ectopic ESCs and normal ESCs treated with plasmid pEGFP‑N1‑IDO1 or SD11‑IDO1 short hairpin RNA were co‑cultured with peripheral blood‑derived monocyte (PBMC)‑driven macrophages directly for 48 h...
February 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28238206/synergistic-effect-of-ddt-and-its-metabolites-in-lipopolysaccharide-mediated-tnf-%C3%AE-production-is-inhibited-by-progesterone-in-peripheral-blood-mononuclear-cells
#4
Pablo Dominguez-Lopez, Laura Diaz-Cueto, Arturo Aguilar-Rojas, Fabian Arechavaleta-Velasco
Increased TNF-α levels have been associated with adverse pregnancy outcomes. Lipopolysaccharide (LPS), 1,1,1-trichloro-2,2-bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE), and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) induce TNF-α release in peripheral blood mononuclear cells (PBMC). Conversely, progesterone (P4) inhibits TNF-α secretion. Pregnant women in malaria endemic areas may be co-exposure to these compounds. Thus, this study was to investigate the synergistic effect of LPS and these pesticides in PBMC and to assess P4 influence on this synergy...
February 26, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28235702/design-synthesis-biological-evaluation-and-x-ray-structural-studies-of-potent-human-dihydroorotate-dehydrogenase-inhibitors-based-on-hydroxylated-azole-scaffolds
#5
Stefano Sainas, Agnese C Pippione, Marta Giorgis, Elisa Lupino, Parveen Goyal, Cristina Ramondetti, Barbara Buccinnà, Marco Piccinini, Rodolpho C Braga, Carolina H Andrade, Mikael Andersson, Ann-Christin Moritzer, Rosmarie Friemann, Stefano Mensa, Salam Al-Kadaraghi, Donatella Boschi, Marco L Lolli
A new generation of potent hDHODH inhibitors designed by a scaffold-hopping replacement of the quinolinecarboxylate moiety of brequinar, one of the most potent known hDHODH inhibitors, is presented here. Their general structure is characterized by a biphenyl moiety joined through an amide bridge with an acidic hydroxyazole scaffold (hydroxylated thiadiazole, pyrazole and triazole). Molecular modelling suggested that these structures should adopt a brequinar-like binding mode involving interactions with subsites 1, 2 and 4 of the hDHODH binding site...
March 31, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28181858/evaluation-of-immunomodulatory-properties-of-feline-mesenchymal-stem-cells
#6
Maciej Parys, John M Kruger, Vilma Yuzbasiyan-Gurkan
Mesenchymal stem cells (MSC) offer a novel approach to treatment of inflammatory disorders in humans and companion animals. Cats spontaneously develop a wide variety of inflammatory disorders and may potentially benefit from MSC-based therapies. Multiple genes are involved in immunomodulation by MSC and interspecies differences between expressions of these genes exist. The goals of the study were to characterize the expression of genes known to be involved in MSC-based immunomodulation and determine the effect of MSC on proliferation of T-cells in co-culture experiments with PBMC...
February 9, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28100035/stromal-cells-act-as-guardians-for-endothelial-progenitors-by-reducing-their-immunogenicity-after-co-transplantation
#7
Naima Souidi, Meaghan Stolk, Juliane Rudeck, Dirk Strunk, Katharina Schallmoser, Hans-Dieter Volk, Martina Seifert
Regeneration of injured tissues requires effective therapeutic strategies supporting vasculogenesis. The lack of instantly available autologous cell sources and immunogenicity of allogeneic endothelial (progenitor) cells limits clinical progress. Based on the immunosuppressive potency of mesenchymal stem/progenitor cells (MSCs), we investigated whether crosstalk between endothelial colony-forming progenitor cells (ECFCs) and MSCs during vasculogenesis could lower allogeneic T cell responses against ECFCs allowing long-term engraftment in vivo...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28075442/increased-expression-of-pd%C3%A2-l1-by-the-human-papillomavirus-16-e7-oncoprotein-inhibits-anticancer-immunity
#8
Chaoqi Liu, Jiao Lu, Huiqun Tian, Wei Du, Lin Zhao, Jing Feng, Ding Yuan, Zhiying Li
Cytotoxic T lymphocyte dysfunction is frequently associated with PD‑L1/PD‑1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)‑induced evasion of cervical cancer cells to the host immune system via the programmed death ligand  1/programmed death 1 (PD‑L1/PD‑1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD‑L1 in cervical tissues was observed when compared with normal cervical tissues...
January 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28045905/human-leukocytes-kill-brugia-malayi-microfilariae-independently-of-dna-based-extracellular-trap-release
#9
Ciaran J McCoy, Barbara J Reaves, Steeve Giguère, Ruby Coates, Balázs Rada, Adrian J Wolstenholme
BACKGROUND: Wuchereria bancrofti, Brugia malayi and Brugia timori infect over 100 million people worldwide and are the causative agents of lymphatic filariasis. Some parasite carriers are amicrofilaremic whilst others facilitate mosquito-based disease transmission through blood-circulating microfilariae (Mf). Recent findings, obtained largely from animal model systems, suggest that polymorphonuclear leukocytes (PMNs) contribute to parasitic nematode-directed type 2 immune responses. When exposed to certain pathogens PMNs release extracellular traps (NETs) in the form of chromatin loaded with various antimicrobial molecules and proteases...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28035385/increased-expression-of-pd-l1-by-the-human-papillomavirus-16-e7-oncoprotein-inhibits-anticancer-immunity
#10
Chaoqi Liu, Jiao Lu, Huiqun Tian, Wei Du, Lin Zhao, Jing Feng, Ding Yuan, Zhiying Li
Cytotoxic T lymphocyte dysfunction is frequently associated with PD‑L1/PD‑1 pathway activation, and is a principal obstacle in cancer therapy. In the present study, the mechanisms underlying the human papillomavirus (HPV)‑induced evasion of cervical cancer cells to the host immune system via the programmed death ligand  1/programmed death 1 (PD‑L1/PD‑1) signaling pathway was investigated. A significant increase in the expression of the HPV16E7 viral protein and PD‑L1 in cervical tissues was observed when compared with normal cervical tissues...
December 23, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27974697/surrogate-in-vitro-activation-of-innate-immunity-synergizes-with-interleukin-7-to-unleash-rapid-antigen-driven-outgrowth-of-cd4-and-cd8-human-peripheral-blood-t-cells-naturally-recognizing-muc1-her2-neu-and-other-tumor-associated-antigens
#11
Latha B Pathangey, Dustin B McCurry, Sandra J Gendler, Ana L Dominguez, Jessica E Gorman, Girish Pathangey, Laurie A Mihalik, Yushe Dang, Mary L Disis, Peter A Cohen
Effective adoptive immunotherapy has proved elusive for many types of human cancer, often due to difficulties achieving robust expansion of natural tumor-specific T-cells from peripheral blood. We hypothesized that antigen-driven T-cell expansion might best be triggered in vitro by acute activation of innate immunity to mimic a life-threatening infection. Unfractionated peripheral blood mononuclear cells (PBMC) were subjected to a two-step culture, first synchronizing their exposure to exogenous antigens with aggressive surrogate activation of innate immunity, followed by γ-chain cytokine-modulated T-cell hyperexpansion...
December 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27930745/the-ebola-interferon-inhibiting-domains-attenuate-and-dysregulate-cell-mediated-immune-responses
#12
Ndongala Michel Lubaki, Patrick Younan, Rodrigo I Santos, Michelle Meyer, Mathieu Iampietro, Richard A Koup, Alexander Bukreyev
Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m)...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27902371/mapping-b-lymphocytes-as-major-reservoirs-of-naturally-occurring-latent-equine-herpesvirus-5-infection
#13
Zelalem Mekuria, Charles El Hage, Nino P Ficorilli, Elizabeth A Washington, James R Gilkerson, Carol Hartley
Equine herpesvirus 5 (EHV5) is a commonly detected gammaherpesvirus which, along with the closely related EHV2, constitute the only two known Percaviruses that infect horses. Apart from detection in horse populations worldwide and the recent publication of the whole genome, there is little known about the biology and pathogenesis of this virus, with many assumptions made by parallels with EHV2. The long-term survival of gammaherpesviruses within infected hosts involves the establishment and maintenance of latency in selected cell and tissues types, particularly lymphocytes...
November 30, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27897109/effect-of-the-modification-of-p24-peptide-antigen-on-dendritic-cell-uptake-and-t-cell-activation
#14
P L Smith, K J Norgate, E Hegarty, N Grageda, E Heelas, M Sommerfelt, T Lange, Arnt-Ove Hovden, B Sørenson, A Dalgleish, M Bodman-Smith
BACKGROUND: Vacc-4x is a candidate therapeutic vaccine consisting of 4 modified peptides based on conserved regions of HIV-1 p24Gag. Vacc4x has been shown to induce long term cellular immunity in immunized infected individuals resulting a reduction in viral load on treatment interruption. OBJECTIVE: Vacc-4x peptides are modified. In this study the effect of modification on uptake of the peptides into PBMC, their subsequent presentation and antigenicity was tested...
November 29, 2016: Current HIV Research
https://www.readbyqxmd.com/read/27859685/cd147-modulates-the-differentiation-of-t-helper-17-cells-in-patients-with-rheumatoid-arthritis
#15
Hui Yang, Jian Wang, Yu Li, Zhen-Jie Yin, Ting-Ting Lv, Ping Zhu, Yan Zhang
The role of CD147 in regulation of rheumatoid arthritis (RA) is not fully elucidated. The aim of this study was to investigate the effect of cell-to-cell contact of activated CD14(+) monocytes with CD4(+) T cells, and the modulatory role of CD147 on T-helper 17 (Th17) cells differentiation in patients with RA. Twenty confirmed active RA patients and twenty normal controls were enrolled. CD4(+) T cells and CD14(+) monocytes were purified by magnetic beads cell sorting. Cells were cultured under different conditions in CD4(+) T cells alone, direct cell-to-cell contact co-culture of CD4(+) and CD14(+) cells, or indirect transwell co-culture of CD4(+) /CD14(+) cells in response to LPS and anti-CD3 stimulation with or without anti-CD147 antibody pretreatments...
January 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27799218/tlr7-agonist-gs-9620-is-a-potent-inhibitor-of-acute-hiv-1-infection-in-human-peripheral-blood-mononuclear-cells
#16
Rujuta A Bam, Derek Hansen, Alivelu Irrinki, Andrew Mulato, Gregg S Jones, Joseph Hesselgesser, Christian R Frey, Tomas Cihlar, Stephen R Yant
GS-9620 is a potent and selective oral Toll-like receptor 7 (TLR7) agonist that directly activates plasmacytoid dendritic cells (pDCs). GS-9620 suppressed hepatitis B virus (HBV) in animal models of chronic infection and transiently activated HIV expression ex vivo in latently infected peripheral blood mononuclear cells (PBMCs) from virally suppressed patients. Currently, GS-9620 is under clinical evaluation for treating chronic HBV infection and for reducing latent reservoirs in virally suppressed HIV-infected patients...
January 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27731508/peripheral-blood-mononuclear-cells-infiltration-downregulates-decidual-faah-activity-in-an-lps-induced-embryo-resorption-model
#17
Manuel Luis Wolfson, Julieta Aisemberg, Fernando Correa, Ana María Franchi
Maternal infections with gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue plays an important role in the establishment of a local inflammatory process that results in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss...
June 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27727130/recombinant-human-lactoferrin-modulates-human-pbmc-derived-macrophage-responses-to-bcg-and-lps
#18
Shen-An Hwang, Marian L Kruzel, Jeffrey K Actor
Lactoferrin, an iron-binding glycoprotein found in mammalian mucosal secretions and granules of neutrophils, possesses several immune modulatory properties. Published reports indicate that lactoferrin enhances the efficacy of the tuberculosis vaccine, BCG (Bacillus Calmette Guerin), both by increasing macrophage and dendritic cell ability to stimulate receptive T cells and by modulating the inflammatory response. This report is the first to demonstrate the effects of a recombinant human lactoferrin (10 μg/mL) on human PBMC derived CD14(+) and CD16(+) macrophages stimulated with a strong (LPS, 10 ng/mL) or weaker (BCG, MOI 1:1) stimulator of inflammation...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27640362/cd14-monocyte-derived-galectin-9-induces-natural-killer-cell-cytotoxicity-in-chronic-hepatitis-c
#19
Akira Nishio, Tomohide Tatsumi, Takatoshi Nawa, Takahiro Suda, Teppei Yoshioka, Yoshiki Onishi, Satoshi Aono, Minoru Shigekawa, Hayato Hikita, Ryotaro Sakamori, Daisuke Okuzaki, Takasuke Fukuhara, Yoshiharu Matsuura, Naoki Hiramatsu, Tetsuo Takehara
Natural killer (NK) cell activation is associated with both liver injury and persistent infection in chronic hepatitis C (CHC); however, the detailed mechanism of this activation has not yet been fully elucidated. Because galectin-9 (Gal-9) has been reported to be increased in the serum and liver tissue of CHC patients, we investigated the function of Gal-9 in NK cell activation in CHC. First, we evaluated the function of Gal-9 on NK cytotoxicity in vitro. Gal-9 treatment resulted in increased cytotoxicity of naïve NK cells, and the Gal-9-activated NK cells demonstrated cytotoxicity toward hepatoma cells and T cells...
January 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27633294/mammalian-cell-cultures-as-models-for-mycobacterium-tuberculosis-human-immunodeficiency-virus-hiv-interaction-studies-a-review
#20
REVIEW
Walter Chingwaru, Richard H Glashoff, Jerneja Vidmar, Petrina Kapewangolo, Samantha L Sampson
Mycobacterium tuberculosis and human immunodeficiency virus (HIV) co-infections have remained a major public health concern worldwide, particularly in Southern Africa. Yet our understanding of the molecular interactions between the pathogens has remained poor due to lack of suitable preclinical models for such studies. We reviewed the use, this far, of mammalian cell culture models in HIV-MTB interaction studies. Studies have described the use of primary human cell cultures, including (1) monocyte-derived macrophage (MDM) fractions of peripheral blood mononuclear cell (PBMC), alveolar macrophages (AM), (2) cell lines such as the monocyte-derived macrophage cell line (U937), T lymphocyte cell lines (CEMx174, ESAT-6-specific CD4(+) T-cells) and an alveolar epithelial cell line (A549) and (3) special models such as stem cells, three dimensional (3D) or organoid cell models (including a blood-brain barrier cell model) in HIV-MTB interaction studies...
September 2016: Asian Pacific Journal of Tropical Medicine
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