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T cell immunity

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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/28550802/mechanism-of-action-of-three-newly-registered-drugs-for-multiple-sclerosis-treatment
#2
REVIEW
Kaja Kasarełło, Agnieszka Cudnoch-Jędrzejewska, Andrzej Członkowski, Dagmara Mirowska-Guzel
Multiple sclerosis (MS) is a disease of suspected autoimmune origin leading to neurodegeneration. The disease pathomechanism is considered to be primarily based on neuroinflammation directed against myelin antigens caused by autoreactive T cells. MS etiology remains still unknown, which makes it difficult to create an efficient therapy, therefore, MS treatment targets mechanisms involved in disease pathology. In this review, we present the mechanism of action of three newly registered drugs for MS. Dimethyl fumarate (DMF) is an agent presenting a broad spectrum of action...
February 22, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28550730/transplantation-of-aire-overexpressing-bone-marrow-derived-dendritic-cells-delays-the-onset-of-type-1-diabetes
#3
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
#4
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/28550659/hyperoxia-provokes-a-time-and-dose-dependent-inflammatory-response-in-mechanically-ventilated-mice-irrespective-of-tidal-volumes
#5
Hendrik J F Helmerhorst, Laura R A Schouten, Gerry T M Wagenaar, Nicole P Juffermans, Joris J T H Roelofs, Marcus J Schultz, Evert de Jonge, David J van Westerloo
BACKGROUND: Mechanical ventilation and hyperoxia have the potential to independently promote lung injury and inflammation. Our purpose was to study both time- and dose-dependent effects of supplemental oxygen in an experimental model of mechanically ventilated mice. METHODS: Healthy male C57Bl/6J mice, aged 9-10 weeks, were intraperitoneally anesthetized and randomly assigned to the mechanically ventilated group or the control group. In total, 100 mice were tracheotomized and mechanically ventilated for either 8 or 12 h after allocation to different settings for the applied fractions of inspired oxygen (FiO2, 30, 50, or 90%) and tidal volumes (7...
December 2017: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#6
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28550203/socs1-is-a-key-molecule-that-prevents-regulatory-t-cell-plasticity-under-inflammatory-conditions
#7
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/28550202/antigen-specific-t-cell-analysis-reveals-that-active-immune-responses-to-%C3%AE-cell-antigens-are-focused-on-a-unique-set-of-epitopes
#8
Junbao Yang, Xiaomin Wen, Hengyu Xu, Nadia Torres-Chinn, Cate Speake, Carla J Greenbaum, Gerald T Nepom, William W Kwok
CD38 is an activation marker that is present on recently activated T cells, but absent on resting memory T cells. In this study, we show that CD45RO(+)CD38(+) β cell Ag-specific CD4(+) T cells were present at higher frequencies in type 1 diabetes subjects compared with those in healthy subjects. These results imply an ongoing β cell immunity years after onset of diabetes and suggest these activated T cells have an active role in the disease process. The Ag specificities of these activated T cells were determined by a novel CD154 T cell epitope mapping assay...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550197/viral-rna-unprimed-rig-i-restrains-stat3-activation-in-the-modulation-of-regulatory-t-cell-th17-cell-balance
#9
Hui Yang, He-Zhou Guo, Xian-Yang Li, Jian Lin, Wu Zhang, Jun-Mei Zhao, Hong-Xin Zhang, Sai-Juan Chen, Zhu Chen, Jiang Zhu
Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4(+) T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I(-/-) CD4(+) T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28550184/reduced-hematopoietic-stem-cells-frequency-predicts-outcome-in-acute-myeloid-leukemia
#10
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/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/28550042/t-cell-expression-of-ahr-inhibits-the-maintenance-of-ptreg-cells-in-the-gi-tract-in-acute-gvhd
#12
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/28549970/distinct-patterns-of-cellular-immune-response-elicited-by-influenza-non-adjuvanted-and-as03-adjuvanted-monovalent-h1n1-pdm09-vaccine
#13
Sarah Giarola-Silva, Jordana G A Coelho-Dos-Reis, Marina Moraes Mourão, Ana Carolina Campi-Azevedo, Erick E Nakagaki Silva, Maria Luiza-Silva, Marina Angela Martins, Amanda Cardoso de Oliveira Silveira Cassette, Maurício Azevedo Batista, Vanessa Peruhype-Magalhães, Lis Ribeiro do Valle Antonelli, José Geraldo Leite Ribeiro, Silvana Maria Elói-Santos, Alexandre Vieira Machado, Andréa Teixeira-Carvalho, Olindo Assis Martins-Filho, Márcio Sobreira Silva Araújo
The study aimed at identifying biomarkers of immune response elicited by non-adjuvanted-(NAV) and adjuvanted-(AV) H1N1(pdm09) vaccines. The results showed that despite both vaccines elicited similar levels of anti-H1N1 antibodies at day30 after vaccination, higher reactivity was observed in AV at day180. While AV induced early changes in cell-surface molecules on monocytes, CD4(+), CD8(+) T-cells and B-cells, NAV triggered minor changes, starting later on at day3. Furthermore, AV induced a late and persistent increase in TLR gene expression after day3, except for tlr4, while NAV displayed earlier but transient tlr3/4/7/9 up-regulation...
May 23, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28549917/dendritic-cell-derived-exosomes-elicit-tumor-regression-in-autochthonous-hepatocellular-carcinoma-mouse-models
#14
Zhen Lu, Bingfeng Zuo, Renwei Jing, Xianjun Gao, Quan Rao, Zhili Liu, Han Qi, Hongxing Guo, HaiFang Yin
BACKGROUND & AIMS: Dendritic cell (DC)-derived exosomes (DEXs) form a new class of vaccines for cancer immunotherapy. However their potency in hepatocellular carcinoma (HCC), a life-threatening malignancy with limited treatment options in the clinic and responds poorly to immunotherapy, remains to be investigated. METHODS: Exosomes derived from α-fetoprotein (AFP) - expressing DCs (DEXAFP) were investigated in three different HCC mouse models systemically and tumor growth and microenvironment were monitored...
May 23, 2017: Journal of Hepatology
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
#15
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/28549714/the-enigmatic-role-of-viruses-in-multiple-sclerosis-molecular-mimicry-or-disturbed-immune-surveillance
#16
REVIEW
Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability...
May 23, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28549586/critical-role-of-hla-dr%C3%AE-binding-peptides-peripheral-flanking-residues-in-fully-protective-malaria-vaccine-development
#17
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
#18
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/28549420/prognostic-significance-of-tumor-infiltrating-immune-cells-in-oral-squamous-cell-carcinoma
#19
Juan Fang, Xiaoxu Li, Da Ma, Xiangqi Liu, Yichen Chen, Yun Wang, Vivian Wai Yan Lui, Juan Xia, Bin Cheng, Zhi Wang
BACKGROUND: Prognostic factors aid in the stratification and treatment of cancer. This study evaluated prognostic importance of tumor infiltrating immune cell in patients with oral squamous cell carcinoma. METHODS: Profiles of infiltrating immune cells and clinicopathological data were available for 78 OSCC patients with a median follow-up of 48 months. The infiltrating intensity of CD8, CD4, T-bet, CD68 and CD57 positive cells were assessed by immunohistochemistry...
May 26, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28548962/prognostic-implication-of-leucocyte-subpopulations-in-diffuse-large-b-cell-lymphoma
#20
Xiao Han, Jing Ruan, Wei Zhang, Daobin Zhou, Dongsheng Xu, Qiang Pei, Mingqi Ouyang, Mengxuan Zuo
BACKGROUND: Recent studies have suggested that variables related to host adaptive immunity and the tumor microenvironment may predict the outcome in patients with non-Hodgkin's lymphoma. This study was undertaken to determine the prognostic value of peripheral blood leucocyte subpopulations in diffuse large-B-cell lymphoma patients. METHODS: We prospectively analyzed the 16 leukocyte subpopulations using Cytodiff flow cytometric technique in a cohort of 45 diffuse large-B-cell lymphoma patients at a single institution between February and December 2014...
May 12, 2017: Oncotarget
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