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https://www.readbyqxmd.com/read/28550816/designing-an-hcv-vaccine-a-unique-convergence-of-prevention-and-therapy
#1
REVIEW
Christopher M Walker
Direct acting antivirals can cure chronic hepatitis C virus (HCV) infection but whether they will reduce global liver disease burden is uncertain. Most chronic infections are undiagnosed and transmission has increased in recent years. The first trial of a preventive vaccine is now underway in humans at risk for HCV infection. It will test the novel hypothesis that T cell-mediated immunity alone can prevent persistent HCV infection. Another vaccine that elicits neutralizing antibodies is at an advanced stage of development...
May 24, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#2
Dongbei Li, Bo Zhao, Yadong Luo, Steven Limbara, Bingjie Zhao, Xueyang Zou, Wei Yang, Yi Li
Autoimmune regulator (Aire) plays an indispensable role in maintaining central immune tolerance by promoting the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs) and dendritic cells (DCs), which lead to the deletion of autoreactive T cells or the induction of Tregs and consequently prevent autoimmune disease development. Curing autoimmune diseases has always been a challenge. DC-based immunotherapy represents a new and effective method to establish tolerance...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550681/antibiotic-associated-manipulation-of-the-gut-microbiota-and-phenotypic-restoration-in-nod-mice
#3
James R Fahey, Bonnie L Lyons, Haiyan L Olekszak, Anthony J Mourino, Jeremy J Ratiu, Jeremy J Racine, Harold D Chapman, David V Serreze, Dina L Baker, N Ken Hendrix
Segmented filamentous bacterium (SFB) a gram-positive, anaerobic, and intestinal commensal organism directly influencesthe development of Th17 helper cells in the small intestine of mice. In NOD mice, SFB colonization interferes with the developmentof type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, suggesting that SFB may influence Th17 cells to inhibit Th1populations associated with the anti-β-cell immune response. This effect is a serious concern for investigators who use NOD micefor diabetes research because the expected incidence of disease decreases markedly when they are colonized by SFB...
May 26, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28550203/socs1-is-a-key-molecule-that-prevents-regulatory-t-cell-plasticity-under-inflammatory-conditions
#4
Reiko Takahashi, Hiroko Nakatsukasa, Shunichi Shiozawa, Akihiko Yoshimura
We previously showed that regulatory T cells (Tregs) from T cell-specific Socs1-deficient mice (Socs1(fl/fl)Lck-Cre(+) mice) easily convert into Th1- or Th17-like cells (ex-Tregs), which lose Foxp3 expression and suppressive functions in vivo. Because Tregs in Socs1(fl/fl)Lck-Cre(+) mice are constantly exposed to a large amount of inflammatory cytokines produced by non-Tregs in vivo, in this study we analyzed Treg-specific Socs1-deficient mice (Socs1(fl/fl)Foxp3(YFP-Cre) mice). These mice developed dermatitis, splenomegaly, and lymphadenopathy that were much milder than those in Socs1(fl/fl)Lck-Cre(+) mice...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550199/comprehensive-approach-for-identifying-the-t-cell-subset-origin-of-cd3-and-cd28-antibody-activated-chimeric-antigen-receptor-modified-t-cells
#5
Michael Schmueck-Henneresse, Bilal Omer, Thomas Shum, Haruko Tashiro, Maksim Mamonkin, Natalia Lapteva, Sandhya Sharma, Lisa Rollins, Gianpietro Dotti, Petra Reinke, Hans-Dieter Volk, Cliona M Rooney
The outcome of therapy with chimeric Ag receptor (CAR)-modified T cells is strongly influenced by the subset origin of the infused T cells. However, because polyclonally activated T cells acquire a largely CD45RO(+)CCR7(-) effector memory phenotype after expansion, regardless of subset origin, it is impossible to know which subsets contribute to the final T cell product. To determine the contribution of naive T cell, memory stem T cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cell populations to the CD3 and CD28-activated CAR-modified T cells that we use for therapy, we followed the fate and function of individually sorted CAR-modified T cell subsets after activation with CD3 and CD28 Abs (CD3/28), transduction and culture alone, or after reconstitution into the relevant subset-depleted population...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550198/host-derived-cd70-suppresses-murine-graft-versus-host-disease-by-limiting-donor-t-cell-expansion-and-effector-function
#6
Nicholas D Leigh, Rachel E O'Neill, Wei Du, Chuan Chen, Jingxin Qiu, Jonathan D Ashwell, Philip L McCarthy, George L Chen, Xuefang Cao
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic and immunologic diseases. However, graft-versus-host disease (GVHD) may develop when donor-derived T cells recognize and damage genetically distinct normal host tissues. In addition to TCR signaling, costimulatory pathways are involved in T cell activation. CD27 is a TNFR family member expressed on T cells, and its ligand, CD70, is expressed on APCs. The CD27/CD70 costimulatory pathway was shown to be critical for T cell function and survival in viral infection models...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550190/patient-derived-anti-%C3%AE-2gp1-antibodies-recognize-a-peptide-motif-pattern-and-not-a-specific-sequence-of-residues
#7
Philippe de Moerloose, Céline Fickentscher, Françoise Boehlen, Jean-Marie Tiercy, Egbert K O Kruithof, Karim J Brandt
Antiphospholipid antibody syndrome is an autoimmune disease characterized by the presence of so-called antiphospholipid antibodies and clinical manifestations such as recurrent thromboembolic or pregnancy complications. Although the main antigenic determinant for antiphospholipid antibodies has been identified as the beta-2-glycoprotein 1 (β2GP1), the precise epitope recognized by antiphospholipid antibodies still remains largely unknown. In the present study, we wanted to identify a sequence in the domain I of β2GP1 able to induce the proliferation of CD4+ T cells isolated from antiphospholipid antibody syndrome patients but not from healthy donors and to interact with antiphospholipid antibodies...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550184/reduced-hematopoietic-stem-cells-frequency-predicts-outcome-in-acute-myeloid-leukemia
#8
Wenwen Wang, Thomas Stiehl, Simon Raffel, Van T Hoang, Isabel Hoffmann, Laura Poisa-Beiro, Borhan R Saeed, Rachel Blume, Linda Manta, Volker Eckstein, Tilmann Bochtler, Patrick Wuchter, Marieke Essers, Anna Jauch, Andreas Trumpp, Anna Marciniak-Czochra, Anthony D Ho, Christoph Lutz
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients that achieved durable remissions...
May 26, 2017: Haematologica
https://www.readbyqxmd.com/read/28550122/the-blood-borne-sialyltransferase-st6gal-1-is-a-negative-systemic-regulator-of-granulopoiesis
#9
Christopher W L Dougher, Alexander Buffone, Michael J Nemeth, Mehrab Nasirikenari, Eric E Irons, Paul N Bogner, Joseph T Y Lau
Responding to systemic demands in producing and replenishing end-effector blood cells is predicated on the appropriate delivery and interpretation of extrinsic signals to the HSPCs. The data presented herein implicate the systemic, extracellular form of the glycosyltransferase ST6Gal-1 in the regulation of late-stage neutrophil development. ST6Gal-1 is typically a membrane-bound enzyme sequestered within the intracellular secretory apparatus, but an extracellular form is released into the blood from the liver...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550121/bcl6-represses-antiviral-resistance-in-follicular-t-helper-cells
#10
Tohti Amet, Young Min Son, Li Jiang, In Su Cheon, Su Huang, Samir K Gupta, Alexander L Dent, Luis J Montaner, Qigui Yu, Jie Sun
Follicular Th (Tfh) cells are a distinct subset of Th cells that help B cells produce class-switched antibodies. Studies have demonstrated that Tfh cells are highly prone to HIV infection and replication. However, the molecular mechanisms underlying this phenomenon are largely unclear. Here, we show that murine and human Tfh cells have diminished constitutive expression of IFN-stimulated genes (ISGs) inclusive of antiviral resistance factor MX dynamin-like GTPase 2 (MX2) and IFN-induced transmembrane 3 (IFITM3) compared with non-Tfh cells...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550117/comparative-exploration-of-multidimensional-flow-cytometry-software-a-model-approach-evaluating-t-cell-polyfunctional-behavior
#11
Timothy T Spear, Michael I Nishimura, Patricia E Simms
Advancement in flow cytometry reagents and instrumentation has allowed for simultaneous analysis of large numbers of lineage/functional immune cell markers. Highly complex datasets generated by polychromatic flow cytometry require proper analytical software to answer investigators' questions. A problem among many investigators and flow cytometry Shared Resource Laboratories (SRLs), including our own, is a lack of access to a flow cytometry-knowledgeable bioinformatics team, making it difficult to learn and choose appropriate analysis tool(s)...
May 26, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28550101/a-novel-experimental-rat-model-of-peripheral-nerve-scarring-reliably-mimicking-post-surgical-complications-and-recurring-adhesions
#12
Angela Lemke, Carina Penzenstadler, James Ferguson, Dominika Lidinsky, Rudolf Hopf, Monika Bradl, Heinz Redl, Susanne Wolbank, Thomas Hausner
Inflammation, fibrosis and perineural adhesions with the surrounding tissue are common pathological processes following nerve injury and surgical interventions on peripheral nerves in human patients. Furthermore, these signs can reoccur following external neurolysis, currently the most common surgical treatment, thus leading to renewed nerve function impairment and chronic pain. To enable a successful evaluation of new therapeutic approaches, it is crucial to use a reproducible animal model that mimics the main clinical symptoms occurring in human patients...
May 26, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28550062/engineering-of-a-hyperthermophilic-archaeon-thermococcus-kodakarensis-that-displays-chitin-dependent-hydrogen-production
#13
Mehwish Aslam, Ayumi Horiuchi, Jan-Robert Simons, Savyasachee Jha, Masahiro Yamada, Toru Odani, Rikako Fujimoto, Yasuyuki Yamamoto, Ryoma Gunji, Tadayuki Imanaka, Tamotsu Kanai, Haruyuki Atomi
Thermococcus kodakarensis is a hyperthermophilic archaeon that harbors a complete set of genes for chitin degradation to fructose 6-phosphate. However, wild-type T. kodakarensis KOD1 does not display growth on chitin. In this study, we developed a T. kodakarensis strain that can grow on chitin via genetic and adaptive engineering. First, a chitinase overproduction strain (KC01) was constructed by replacing the chitinase gene promoter with a strong promoter from the cell-surface glycoprotein gene, resulting in increased degradation of swollen chitin and accumulation of N-, N'-diacetylchitobiose in the medium...
May 26, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28550045/pacsin2-accelerates-nephrin-trafficking-and-is-up-regulated-in-diabetic-kidney-disease
#14
Vincent Dumont, Tuomas A Tolvanen, Sara Kuusela, Hong Wang, Tuula A Nyman, Sonja Lindfors, Jukka Tienari, Harry Nisen, Shiro Suetsugu, Markus Plomann, Hiroshi Kawachi, Sanna Lehtonen
Nephrin is a core component of podocyte (glomerular epithelial cell) slit diaphragm and is required for kidney ultrafiltration. Down-regulation or mislocalization of nephrin has been observed in diabetic kidney disease (DKD), characterized by albuminuria. Here, we investigate the role of protein kinase C and casein kinase 2 substrate in neurons 2 (PACSIN2), a regulator of endocytosis and recycling, in the trafficking of nephrin and development of DKD. We observe that PACSIN2 is up-regulated and nephrin mislocalized in podocytes of obese Zucker Diabetic Fatty (ZDF) rats that have altered renal function...
May 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28550042/t-cell-expression-of-ahr-inhibits-the-maintenance-of-ptreg-cells-in-the-gi-tract-in-acute-gvhd
#15
Trisha A Dant, Kaifeng L Lin, Danny W Bruce, Stephanie A Montgomery, Oleg V Kolupaev, Hemamalini Bommiasamy, Lisa M Bixby, John T Woosley, Karen P McKinnon, Frank J Gonzalez, Bruce R Blazar, Benjamin G Vincent, James M Coghill, Jonathan S Serody
The Aryl-hydrocarbon-receptor (AhR) is a ligand-activated transcription factor that affects the function and development of immune cells. Here, we show that recipient mice receiving AhR(-/-) T cells have improved survival and decreased acute graft versus host disease (aGvHD) in two different murine allogeneic bone marrow transplant models (BMT). We also show that CD4(+) T cells lacking AhR demonstrate reduced accumulation in secondary lymphoid tissue due to low levels of proliferation 4 days after BMT. Additionally, we found a significant increase in the quantity of peripherally induced regulatory donor T cells (pTregs) in the colon of recipients transplanted with AhR(-/-) T cells 14 days after transplant...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549988/regulatory-t-cell-populations-in-children-are-affected-by-age-and-food-allergy-diagnosis
#16
Benjamin T Prince, Ashley L Devonshire, Kristin A Erickson, Jenna Bergerson, Dalia Fuleihan, Christine Szychlinski, Robert P Schleimer, Paul J Bryce, Anne Marie Singh
Young food allergic children have decreased regulatory T cell (Treg) percentages. Only Tregs from healthy controls demonstrated age-related increases in their expression of the gut-associated chemokine receptor CCR6, which may be important in maintaining oral tolerance to foods and preventing the development of allergic disease.
May 23, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28549876/prediction-and-analysis-of-promiscuous-t-cell-epitopes-derived-from-the-vaccine-candidate-antigens-of-leishmania-donovani-binding-to-mhc-class-ii-alleles-using-in-silico-approach
#17
Manju Kashyap, Varun Jaiswal, Umar Farooq
Visceral leishmaniasis is a dreadful infectious disease and caused by the intracellular protozoan parasites, Leishmania donovani and Leishmania infantum. Despite extensive efforts for developing effective prophylactic vaccine, still no vaccine is available against leishmaniasis. However, advancement in immunoinformatics methods generated new dimension in peptide based vaccine development. The present study was aimed to identify T-cell epitopes from the vaccine candidate antigens like Lipophosphogylcan-3(LPG-3) and Nucleoside hydrolase (NH) from the L...
May 23, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28549586/critical-role-of-hla-dr%C3%AE-binding-peptides-peripheral-flanking-residues-in-fully-protective-malaria-vaccine-development
#18
César Reyes, Rocío Rojas-Luna, Jorge Aza-Conde, Luisa Tabares, Manuel A Patarroyo, Manuel E Patarroyo
A vaccine candidate component must fit perfectly into the antigen presenting HLA-DRβ* molecule's groove (or canonical nonapeptide) peptide binding region (PBR) during antigen presentation for proper presentation to the T-cell receptor (TCR), conforming a specific and stable macromolecular complex and induce an appropriate immune response. Antigen's peripheral flanking residues (PFR, positions (p) -p2 and p10) must thus establish strong interactions with the HLA-DRβ* - TCR complex. These amino acids (aa) have specific physico-chemical characteristics enabling differentiation between non-protective but antibody-inducer (NPAI), short-lived protection inducer (SLPI) and long-lasting protection inducer (LLPI) peptides when used as an antimalarial vaccine component...
May 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28549432/dendritic-cells-combined-with-tumor-cells-and-%C3%AE-galactosylceramide-induce-a-potent-therapeutic-and-nk-cell-dependent-antitumor-immunity-in-b-cell-lymphoma
#19
Laura Escribà-Garcia, Carmen Alvarez-Fernández, Marta Tellez-Gabriel, Jorge Sierra, Javier Briones
BACKGROUND: Invariant natural killer T (iNKT) cells are a small population of lymphocytes with unique specificity for glycolipid antigens presented by non-polymorphic CD1d receptor on dendritic cells (DCs). iNKT cells play a central role in tumor immunology since they are implicated in the coordination of innate and adaptive immune responses. These cells can be activated with the prototypic lipid α-galactosylceramide (α-GalCer), stimulating interferon gamma (IFN-γ) production and cytokine secretion, which contribute to the enhancement of T cell activation...
May 26, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28549385/identification-and-imaging-of-leukemia-cells-using-dual-aptamer-functionalized-graphene-oxide-complex
#20
Amirhossein Bahreyni, Rezvan Yazdian-Robati, Mohammad Ramezani, Mehdi Rasouli, Morteza Alinezhad Nameghi, Mona Alibolandi, Khalil Abnous, Seyed Mohammad Taghdisi
Acute lymphoblastic leukemia is the most common malignancy in children. Patient improvement completely depends on the diagnosis of acute lymphoblastic leukemia. So there is a great demand for diagnosis of acute lymphoblastic leukemia. In this study, a novel assay based on dual-aptamer (Sgc8c and ATP aptamers)-functionalized graphene oxide (DAFGO) complex was designed for the identification of Molt-4 cells (human acute lymphoblastic leukemia T-cell). This assay relies on the internalization of DAFGO complex into Molt-4 cells, but not into U266 cells, using Sgc8c aptamer as molecular recognition probe, and release of FAM-labeled ATP aptamer from the complex in the presence of high amounts of ATP in lysosome, leading to a strong fluorescence emission...
January 1, 2017: Journal of Biomaterials Applications
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