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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/28319404/encapsulation-of-an-ep67-conjugated-ctl-peptide-vaccine-in-nanoscale-biodegradable-particles-increases-the-efficacy-of-respiratory-immunization-and-affects-the-magnitude-and-memory-subsets-of-vaccine-generated-mucosal-and-systemic-cd8-t-cells-in-a-diameter
#2
Bala Vamsi Krishna Karuturi, Shailendra B Tallapaka, Pravin Yeapuri, Stephen M Curran, Sam D Sanderson, Joseph A Vetro
The diameter of biodegradable particles used to co-encapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8(+) T cells generated by systemic immunization. Possible effects on the magnitude of CD8(+) T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles...
March 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28296380/cd62l-is-not-a-reliable-biomarker-for-predicting-pml-risk-in-natalizumab-treated-r-ms-patients-author-response
#3
COMMENT
Ellen Cahir-McFarland, Richard M Ransohoff, Linda Lieberman, Tatiana Plavina
No abstract text is available yet for this article.
August 30, 2016: Neurology
https://www.readbyqxmd.com/read/28294319/grpr-antagonist-protects-from-drug-induced-liver-injury-by-impairing-neutrophil-chemotaxis-and-motility
#4
Rafael S Czepielewski, Natália Jaeger, Pedro E Marques, Maísa M Antunes, Maurício M Rigo, Débora M Alvarenga, Rafaela V Pereira, Rodrigo D da Silva, Tiago G Lopes, Vinícius D da Silva, Bárbara N Porto, Gustavo B Menezes, Cristina Bonorino
Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXCR2 ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration and mechanisms underlying this phenomenon...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28272395/a-possible-role-for-neutrophils-in-allergic-rhinitis-revealed-after-cellular-subclassification
#5
Julia Arebro, Sandra Ekstedt, Eric Hjalmarsson, Ola Winqvist, Susanna Kumlien Georén, Lars-Olaf Cardell
A re-examination of former concepts is required to meet today's medical challenges in allergic rhinitis. Previously, neutrophils have been treated as a relatively homogenous cell population found in the nose both when the patient is suffering at the height of the allergic season as well as when the patient report no symptoms. However, new data indicates that neutrophils can be divided into different subsets with diverse roles in inflammation. We showed increased levels of neutrophils in peripheral blood, nasal biopsies and nasal lavage fluid (NAL) from allergic patients during the pollen season compared to healthy controls...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28247912/net-producing-cd16-high-cd62l-dim-neutrophils-migrate-to-tumor-sites-and-predict-improved-survival-in-patients-with-hnscc
#6
Camilla Rydberg Millrud, Åsa Kågedal, Susanna Kumlien Georén, Ola Winqvist, Rolf Uddman, Ronia Razavi, Eva Munck-Wikland, Lars Olaf Cardell
The concept of functional neutrophil subsets is new and their clinical significance in malignancies is unknown. Our study investigated the role of CD16(dim) CD62L(high) , CD16(high) CD62L(high) and CD16(high) CD62L(dim) neutrophil subsets in head and neck squamous cell carcinoma (HNSCC) patients. These neutrophil subsets may play different roles in immune-related activity in cancer, based on their profile, activation state and migration ability within a tumor site, which may be important in predicting cancer prognoses...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28242002/canine-peripheral-blood-cd4-cd8-double-positive-tcell-subpopulations-exhibit-distinct-tcell-phenotypes-and-effector-functions
#7
Kathrin Rothe, Doris Bismarck, Mathias Büttner, Gottfried Alber, Heiner von Buttlar
Canine peripheral blood CD4(+)CD8α(+) double-positive (dp) Tcells represent a small population of T lymphocytes that are not only derived from single-positive (sp) CD4(+) but also from CD8(+) Tcells. Dp Tcells can be subdivided in three different subpopulations according to their expression levels of CD4 and CD8α, i.e. the CD4(dim)CD8α(bright), CD4(bright)CD8α(bright), and the CD4(bright)CD8α(dim) subsets. Previously we could show that total canine peripheral CD4(+)CD8α(+) dp Tcells have features of activated Tcells...
March 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28239467/ccr7-selected-gene-modified-t-cells-maintain-a-central-memory-phenotype-and-display-enhanced-persistence-in-peripheral-blood-in-vivo
#8
Gray Kueberuwa, Hannah Gornall, Erik Marcelo Alcantar-Orozco, Deborah Bouvier, Zainul Abedin Kapacee, Robert Edward Hawkins, David Edward Gilham
BACKGROUND: Adoptive T cell immunotherapy (ATCT) for cancer entails infusing patients with T cells that recognise and destroy tumour cells. Efficient engraftment of T cells and persistence in the circulation correlate with favourable clinical outcomes. T cells of early differentiation possess an increased capacity for proliferation and therefore persistence, using these cells for ATCT could therefore lead to improved clinical outcomes. METHOD: We describe a method to enrich T cells of early differentiation status using paramagnetic beads and antibodies targeting cells expressing C-C motif chemokine receptor 7 (CCR7)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28224362/analysis-of-foxp3-regulatory-t-cell-subpopulations-in-peripheral-blood-and-tissue-of-patients-with-systemic-lupus-erythematosus
#9
Angelika Schmidt, Cosima C Rieger, Ram Kumar Venigalla, Szabolcs Éliás, Regina Max, Hanns-Martin Lorenz, Hermann-Josef Gröne, Peter H Krammer, Annegret Kuhn
Regulatory T cells (Tregs) are critical mediators of immune tolerance, yet their involvement in the autoimmune disease systemic lupus erythematosus (SLE) is incompletely understood. We analyzed CD4(+) T cell subpopulations with Treg-related phenotypes and their association with disease activity in peripheral blood (PB) and tissues of patients with SLE. In detail, we quantified subpopulations regarding CD25, FOXP3, CD62L, CCR6, CD27, CD45RA, and CD45RO expression in PB from 31 patients with SLE divided into two disease activity groups and 32 healthy controls using flow cytometry...
February 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28224232/effects-of-traumeel-tr14-on-recovery-and-inflammatory-immune-response-after-repeated-bouts-of-exercise-a-double-blind-rct
#10
RANDOMIZED CONTROLLED TRIAL
Kerstin Muders, Christian Pilat, Vanessa Deuster, Torsten Frech, Karsten Krüger, Jörn Pons-Kühnemann, Frank-Christoph Mooren
PURPOSE: The purpose of this double-blind, randomized, placebo-controlled clinical trial was to investigate the effects of the natural combination medicine Traumeel (Tr14) consisting of 14 diluted biological and mineral components on the inflammatory immune response and recovery up to 72 h after repetitive bouts of bicycle tests. METHODS: Antigen-stimulated IL-1ra and IL-6 were defined as primary outcome measures. Moreover, various immunological and serum muscle damage markers were investigated...
March 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28194759/association-of-peripheral-nk-cell-counts-with-helios-ifny-tregs-in-patients-with-good-long-term-renal-allograft-function
#11
Karina Trojan, Li Zhu, Mostafa Aly, Rolf Weimer, Nuray Bulut, Christian Morath, Gerhard Opelz, Volker Daniel
BACKGROUND: Little is known about a possible interaction of NK cells with Tregs in long-term stable kidney transplant recipients. METHODS: Absolute counts of lymphocyte and Treg subsets were studied in whole blood samples of 136 long-term stable renal transplant recipients and 52 healthy controls using eight-color-fluorescence flow cytometry. Patients were 1946±2201 days (153-10268 days) posttransplant and showed a serum creatinine of 1.7±0.7 mg/dl. RESULTS: Renal transplant recipients investigated >1...
February 14, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28190771/obesity-induced-metabolic-stress-leads-to-biased-effector-memory-cd4-t-cell-differentiation-via-pi3k-p110%C3%AE-akt-mediated-signals
#12
Claudio Mauro, Joanne Smith, Danilo Cucchi, David Coe, Hongmei Fu, Fabrizia Bonacina, Andrea Baragetti, Gaia Cermenati, Donatella Caruso, Nico Mitro, Alberico L Catapano, Enrico Ammirati, Maria P Longhi, Klaus Okkenhaug, Giuseppe D Norata, Federica M Marelli-Berg
Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4(+) T cells. Memory CD4(+) T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28164171/diminished-cd103-%C3%AE-e%C3%AE-7-expression-on-resident-t-cells-from-the-female-genital-tract-of-hiv-positive-women
#13
David C Moylan, Paul A Goepfert, Mirjam-Colette Kempf, Michael S Saag, Holly E Richter, Jiri Mestecky, Steffanie Sabbaj
BACKGROUND: Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT). METHODS: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103(+)CD69(+) CD4(+) and CD8(+) T cells in mucosa-derived T cells from healthy and HIV-positive women. RESULTS: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women...
October 2016: Pathogens & Immunity
https://www.readbyqxmd.com/read/28151427/pd-1-modulates-regulatory-t-cell-homeostasis-during-low-dose-il-2-therapy
#14
Takeru Asano, Yusuke Meguri, Takanori Yoshioka, Yuriko Kishi, Miki Iwamoto, Makoto Nakamura, Yasuhisa Sando, Hideo Yagita, John Koreth, Haesook T Kim, Edwin P Alyea, Philippe Armand, Corey S Cutler, Vincent T Ho, Joseph H Antin, Robert J Soiffer, Yoshinobu Maeda, Mitsune Tanimoto, Jerome Ritz, Ken-Ichi Matsuoka
CD4+Foxp3+ regulatory T cells (Tregs) play a central role in the maintainance of immune tolerance after HSCT. We previously reported that low-dose IL-2 therapy increased circulating Tregs and improved clinical symptoms of chronic GVHD, however, the mechanisms which regulate Treg homeostasis during IL-2 therapy have not been well studied. To elucidate these regulatory mechanisms, we examined the role of inhibitory coreceptors on Tregs during IL-2 therapy in a murine model and in patients with chronic GVHD. Murine studies demonstrated that low-dose IL-2 selectively increased Treg and simultaneously enhanced the expression of Programmed death-1 (PD-1), especially on CD44(+)CD62L(+) central-memory Treg, while expression of other inhibitory molecules including CTLA-4, LAG-3 and TIM-3 remained stable...
February 1, 2017: Blood
https://www.readbyqxmd.com/read/28148734/cutting-edge-helicobacter-pylori-induces-nuclear-hypersegmentation-and-subtype-differentiation-of-human-neutrophils-in-vitro
#15
Laura C Whitmore, Megan N Weems, Lee-Ann H Allen
Helicobacter pylori infects the human stomach and causes a spectrum of disease that includes gastritis, peptic ulcers, and gastric adenocarcinoma. A chronic, neutrophil-rich inflammatory response characterizes this infection. It is established that H. pylori stimulates neutrophil chemotaxis and a robust respiratory burst, but other aspects of this interaction are incompletely defined. We demonstrate here that H. pylori induces N1-like subtype differentiation of human neutrophils as indicated by profound nuclear hypersegmentation, a CD62L(dim), CD16(bright), CD11b(bright), CD66b(bright), CD63(bright) surface phenotype, proinflammatory cytokine secretion, and cytotoxicity...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28112745/a-high-migratory-capacity-of-donor-t-cells-in-response-to-the-lymph-node-homing-receptor-ccr7-increases-the-incidence-and-severity-of-gvhd
#16
I Portero-Sainz, V Gómez-García de Soria, C Cuesta-Mateos, C Fernández-Arandojo, L Vega-Piris, M Royg, B Colom-Fernández, A Marcos-Jiménez, B Somovilla-Crespo, A Ramírez-Mengíbar, V López-Huete, A de Rosendo-Serrano, A Kreutzman, C Muñoz-Calleja
The pathogenesis of GvHD involves migration of donor T-cells into the secondary lymphoid organs in the recipient, which is steered by two homing molecules, CD62L and CCR7. Therefore, we investigated whether the migratory capacity of donor T-cells is associated with GvHD. This single center prospective study included 85 donor-recipient pairs. In vitro chemotaxis assays of the lymphocytes of the apheresis product were performed in parallel to the analysis of CD62L and CCR7 by flow cytometry. The migratory index to the CCR7 ligands, CCL19 and CCL21, was higher in T-cells from donors whose recipients will develop GvHD...
January 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28108544/the-interplay-between-neutrophils-and-cd8-t-cells-improves-survival-in-human-colorectal-cancer
#17
Valeria Governa, Emanuele Trella, Valentina Mele, Luigi Tornillo, Francesca Amicarella, Eleonora Cremonesi, Maunele Giuseppe Muraro, Hui Xu, Raoul Droeser, Silvio Raffael Däster, Martin Bolli, Raffaele Rosso, Daniel Oertli, Serenella Eppenberger-Castori, Luigi Terracciano, Giandomenica Iezzi, Giulio C Spagnoli
PURPOSE: Tumor infiltration by different T lymphocyte subsets is known to be associated with favorable prognosis in colorectal cancer (CRC). Still debated is the role of innate immune system. We investigated clinical relevance, phenotypes and functional features of CRC infiltrating CD66b+ neutrophils and their crosstalk with CD8+ T cells. EXPERIMENTAL DESIGN: CD66b+ and CD8+ cell infiltration was analyzed by immunohistochemistry on a tissue microarray including >650 evaluable CRC samples...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108365/neutrophil-subset-responses-in-infants-with-severe-viral-respiratory-infection
#18
Bart Cortjens, Sarah A Ingelse, Job C Calis, Alexander P Vlaar, Leo Koenderman, Reinout A Bem, Job B van Woensel
Neutrophils are the predominant inflammatory cells recruited to the respiratory tract as part of the innate immune response to viral infections. Recent reports indicate the existence of distinct functional neutrophil subsets in the circulatory compartment of adults, following severe inflammatory conditions. Here, we evaluated the occurrence of neutrophil subsets in blood and broncho-alveolar lavage fluid during severe viral respiratory infection in infants based on CD16/CD62L expression. We show that during the course of severe respiratory infection infants may develop four heterogeneous neutrophil subsets in blood (mature, immature, progenitor, and suppressive neutrophils), each with distinct activation states...
January 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28107375/narcolepsy-type-1-is-associated-with-a-systemic-increase-and-activation-of-regulatory-t-cells-and-with-a-systemic-activation-of-global-t-cells
#19
Michel Lecendreux, Guillaume Churlaud, Fabien Pitoiset, Armelle Regnault, Tu Anh Tran, Roland Liblau, David Klatzmann, Michelle Rosenzwajg
Narcolepsy is a rare neurologic disorder characterized by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep patterns. Narcolepsy type 1 (NT1) has been shown to result from a selective loss of hypothalamic hypocretin-secreting neurons with patients typically showing low CSF-hypocretin levels (<110 pg/ml). This specific loss of hypocretin and the strong association with the HLA-DQB1*06:02 allele led to the hypothesis that NT1 could be an immune-mediated pathology. Moreover, susceptibility to NT1 has recently been associated with several pathogens, particularly with influenza A H1N1 virus either through infection or vaccination...
2017: PloS One
https://www.readbyqxmd.com/read/28098193/non-pathogenic-tissue-resident-cd8-t-cells-uniquely-accumulate-in-the-brains-of-lupus-prone-mice
#20
Peter A Morawski, Chen-Feng Qi, Silvia Bolland
Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining to discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8(+) T cells relative to other lymphocytes in brain tissue, which correlates with lupus disease and limited neuropathology. This is in contrast to all other affected organs, where infiltrating CD4(+) cells are predominant. Brain-infiltrating CD8(+) T cells represent an activated subset of those found in the periphery, having a resident-memory phenotype (CD69(+)CD122(-)PD1(+)CD44(+)CD62L(-)) and expressing adhesion molecules (VLA-4(+)LFA-1(+)) complementary to activated brain endothelium...
January 18, 2017: Scientific Reports
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