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https://www.readbyqxmd.com/read/28719652/long-term-follow-up-of-human-t-cell-responses-to-conserved-hiv-1-regions-elicited-by-dna-simian-adenovirus-mva-vaccine-regimens
#1
Nathifa Moyo, Nicola J Borthwick, Edmund G Wee, Silvia Capucci, Alison Crook, Lucy Dorrell, Tomáš Hanke
BACKGROUND: Durability of vaccine-elicited immune responses is one of the key determinants for vaccine success. Our aim is to develop a vaccination strategy against the human immunodeficiency virus type 1 (HIV-1), which induces protective and durable CD8+ T-cell responses. The central theorem of our approach is to focus T cells on highly conserved regions of the HIV-1 proteome and this is achieved through the use of the first-generation conserved vaccine immunogen HIVconsv. This immunogen vectored by plasmid DNA, simian adenovirus and poxvirus MVA was tested in healthy, HIV-1-negative adults in UK and induced high magnitudes of HIVconsv-specific plurifunctional CD8+ T cells capable of in vitro HIV-1 inhibition...
2017: PloS One
https://www.readbyqxmd.com/read/28719012/the-impact-of-immunoglobulin-in-acute-hiv-infection-on-the-hiv-reservoir-a-randomized-controlled-trial
#2
J Tiraboschi, S Ray, K Patel, A Teague, M Pace, P Phalora, N Robinson, E Hopkins, J Meyerowitz, Y Wang, J Cason, S Kaye, J Sanderson, P Klenerman, S Fidler, J Frater, J Fox
OBJECTIVES: Antiretroviral therapy (ART) during acute HIV infection (AHI) restricts the HIV reservoir, but additional interventions are necessary to induce a cure. Intravenous immunoglobulin (IVIG) is not HIV-specific but is safe and temporarily reduces the HIV reservoir in chronic HIV infection. We present a randomized controlled trial to investigate whether IVIG plus ART in AHI reduces the HIV reservoir and immune activation compared with ART alone. METHODS: Ten men with AHI (Fiebig II-IV) initiated ART (tenofovir, entricitabine, ritonavir boosted darunavir and raltegravir) at HIV-1 diagnosis and were randomized to ART alone or ART plus 5 days of IVIG, once virally suppressed (week 19)...
July 18, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28718943/hepatitis-e-virus-orf-1-induces-proliferative-and-functional-t-cell-responses-in-patients-with-ongoing-and-resolved-hepatitis-e
#3
Jana Al-Ayoubi, Patrick Behrendt, Birgit Bremer, Pothakamuri Venkata Suneetha, Anett Gisa, Franziska Rinker, Michael P Manns, Markus Cornberg, Heiner Wedemeyer, Anke R M Kraft
BACKGROUND AND AIMS: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis with > 3 million symptomatic cases per year accounting for 70,000 HEV-related deaths. HEV-specific T-cell responses have been investigated against structural proteins expressed by open reading frames (ORF) 2 and 3. T-cell responses against non-structural HEV proteins encoded by ORF1 are hardly studied. The aim of this study was to determine HEV ORF1-specific T-cell responses in comparison to ORF2/3 in patients exposed to HEV...
July 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28718360/inflammatory-myopathy-in-horses-with-chronic-piroplasmosis
#4
Maria P Pasolini, Teresa B Pagano, Alessandro Costagliola, Davide De Biase, Barbara Lamagna, Luigi Auletta, Gerardo Fatone, Michele Greco, Pierpaolo Coluccia, Veneziano Veneziano, Claudio Pirozzi, Giuseppina Mattace Raso, Pasquale Santoro, Giuseppe Manna, Serenella Papparella, Orlando Paciello
Horses affected by chronic piroplasmosis may develop poor performance and muscle atrophy. Here we investigate the pathological and immunopathological aspects of myopathy occurring in chronic equine piroplasmosis. The study included 16 horses serologically positive for equine piroplasms presenting with clinical signs and supporting serum biochemical evidence of a myopathy. Skeletal muscle was evaluated by histopathology, immunohistochemistry, indirect immunofluorescence, and molecular detection of piroplasms and inflammatory cytokines in skeletal muscle...
January 1, 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28718069/neurological-involvement-in-patients-with-acute-recent-hiv-1-infection-a-case-control-study
#5
Juan Ambrosioni, Francisca Artigues, David Nicolás, Judit Peñafiel, Fernando Agüero, Christian Manzardo, María Mar Mosquera, Sonsoles Sánchez-Palomino, Elisa De Lazzari, María A Marcos, Montserrat Plana, José M Miró
Primary HIV-1 infection is a relevant period for its virological and epidemiological consequences. Most patients present a symptomatic disease that can be potentially serious, but neurological involvement during primary HIV-1 infection has been poorly studied. The aim of this study was to describe the characteristics and outcomes of primary HIV-1 infection patients presenting neurological symptoms and to compare them with primary HIV-1 infection patients without neurological involvement. Retrospective case-control study (1:3) comparing primary HIV-1 infection patients with and without neurological involvement enrolled in the Acute/Recent Hospital Clinic PHI Cohort between 1997 and 2016...
July 17, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28718065/structure-function-relationships-of-protein-lipopeptide-complexes-and-influence-on-immunogenicity
#6
Acep R Wijayadikusumah, Lucy C Sullivan, David C Jackson, Brendon Y Chua
The lipopeptide, R4Pam2Cys, associates electrostatically with soluble protein antigens and significantly enhances their ability to induce protective humoral and cell-mediated responses. We demonstrate that antibody titers elicited by the antigen ovalbumin (OVA) associated with R4Pam2Cys are higher than those elicited by OVA in the presence of alum and comparable to those elicited by OVA formulated with complete Freund's adjuvant (CFA). The hierarchy of anti-OVA antibody avidities was CFA > R4Pam2Cys = alum...
July 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28717940/alopecia-areata-a-comprehensive-review-of-pathogenesis-and-management
#7
REVIEW
Ralph M Trüeb, Maria Fernanda Reis Gavazzoni Dias
Alopecia areata is a common hair loss condition that is characterized by acute onset of non-scarring hair loss in usually sharply defined areas ranging from small patches to extensive or less frequently diffuse involvement. Depending on its acuity and extent, hair loss is an important cause of anxiety and disability. The current understanding is that the condition represents an organ-specific autoimmune disease of the hair follicle with a genetic background. Genome-wide association studies provide evidence for the involvement of both innate and acquired immunity in the pathogenesis, and mechanistic studies in mouse models of alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFNγ, IFNγ-induced chemokines and cytotoxic CD8 T cells as the main drivers of disease pathogenesis...
July 17, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28717398/preclinical-evaluation-of-nf-%C3%AE%C2%BAb-triggered-dendritic-cells-expressing-the-viral-oncogenic-driver-of-merkel-cell-carcinoma-for-therapeutic-vaccination
#8
Kerstin F Gerer, Michael Erdmann, Sine R Hadrup, Rikke Lyngaa, Lena-Marie Martin, Reinhard E Voll, Beatrice Schuler-Thurner, Gerold Schuler, Niels Schaft, Stefanie Hoyer, Jan Dörrie
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host's genome. Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. METHODS: Cytokine-matured monocyte-derived DCs of healthy donors and MCC patients were electroporated with mRNA encoding the truncLT...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28717140/common-variants-of-t-cells-contribute-differently-to-phenotypic-variation-in-sarcoidosis
#9
Natalia V Rivera, Michael Hagemann-Jensen, Manuel A R Ferreira, Susanna Kullberg, Anders Eklund, Nicholas G Martin, Leonid Padyukov, Johan Grunewald
The involvement of the immune system, particularly the role of T-cells, in sarcoidosis is unclear. The existence of higher CD4+ T-cells and increased CD4/CD8 ratio may indicate a pathogenic role of T-cells in the disease. In this study, we quantified the contribution of T-cells associated variants and of CD4/CD8 ratio in sarcoidosis phenotypes, Löfgren's syndrome (LS) and non- Löfgren's syndrome (non-LS). We employed a polygenic-based approach using genome-wide association studies results on relative levels of T-cells in healthy individuals to measure the genetic contribution of T-cells in sarcoidosis entities...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716933/cortical-actin-recovery-at-the-immunological-synapse-leads-to-termination-of-lytic-granule-secretion-in-cytotoxic-t-lymphocytes
#10
Alex T Ritter, Senta M Kapnick, Sricharan Murugesan, Pamela L Schwartzberg, Gillian M Griffiths, Jennifer Lippincott-Schwartz
CD8(+) cytotoxic T lymphocytes (CTLs) eliminate virally infected cells through directed secretion of specialized lytic granules. Because a single CTL can kill multiple targets, degranulation must be tightly regulated. However, how CTLs regulate the termination of granule secretion remains unclear. Previous work demonstrated that centralized actin reduction at the immune synapse precedes degranulation. Using a combination of live confocal, total internal reflection fluorescence, and superresolution microscopy, we now show that, after granule fusion, actin recovers at the synapse and no further secretion is observed...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716890/negative-regulation-of-cytokine-signaling-in-immunity
#11
Akihiko Yoshimura, Minako Ito, Shunsuke Chikuma, Takashi Akanuma, Hiroko Nakatsukasa
Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4(+) T cells and the maturation of CD8(+) T cells...
July 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28716576/tlr9-mediated-conditioning-of-liver-environment-is-essential-for-successful-intrahepatic-immunotherapy-and-effective-memory-recall
#12
Marcin Cebula, Mathias Riehn, Upneet Hillebrand, Ramona F Kratzer, Florian Kreppel, Georgia Koutsoumpli, Toos Daemen, Hansjörg Hauser, Dagmar Wirth
Immune defense against hepatotropic viruses such as hepatitis B (HBV) and hepatitis C (HCV) poses a major challenge for therapeutic approaches. Intrahepatic cytotoxic CD8 T cells that are crucial for an immune response against these viruses often become exhausted resulting in chronic infection. We elucidated the T cell response upon therapeutic vaccination in inducible transgenic mouse models in which variable percentages of antigen-expressing hepatocytes can be adjusted, providing mosaic antigen distribution and reflecting the varying viral antigen loads observed in patients...
July 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#13
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28716137/progressive-hypoventilation-due-to-mixed-cd8-and-cd4-lymphocytic-polymyositis-following-tremelimumab-durvalumab-treatment
#14
Sooraj John, Scott J Antonia, Trevor A Rose, Robert P Seifert, Barbara A Centeno, Aaron S Wagner, Ben C Creelan
BACKGROUND: The combination of CTLA-4 and PD-L1 inhibitors has a manageable adverse effect profile, although rare immune-related adverse events (irAE) can occur. CASE PRESENTATION: We describe an autoimmune polymyositis following a partial response to combination tremelimumab and durvalumab for the treatment of recurrent lung adenocarcinoma. Radiography revealed significant reduction in all metastases; however, the patient developed progressive neuromuscular hypoventilation due to lymphocytic destruction of the diaphragmatic musculature...
July 18, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28715493/host-genetics-play-a-critical-role-in-controlling-cd8-t-cell-function-and-lethal-immunopathology-during-chronic-viral-infection
#15
Allison F Christiaansen, Megan E Schmidt, Stacey M Hartwig, Steven M Varga
Effective CD8 T cell responses are vital for the control of chronic viral infections. Many factors of the host immune response contribute to the maintenance of effector CD8 T cell responses versus CD8 T cell exhaustion during chronic infection. Specific MHC alleles and the degree of MHC heterogeneity are associated with enhanced CD8 T cell function and viral control during human chronic infection. However, it is currently unclear to what extent host genetics influences the establishment of chronic viral infection...
July 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28715455/synthetic-melanin-bound-to-subunit-vaccine-antigens-significantly-enhances-cd8-t-cell-responses
#16
Antoine F Carpentier, Frédéric Geinguenaud, Thi Tran, Floraly Sejalon, Antoine Martin, Laurence Motte, Eric Tartour, Claire Banissi
Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides...
2017: PloS One
https://www.readbyqxmd.com/read/28715277/superantigen-staphylococcal-enterotoxin-c1-inhibits-the-growth-of-bladder-cancer
#17
Tao Liu, Lin Li, Lei Yin, Hongyuan Yu, Hongwei Jing, Yang Liu, Chuize Kong, Mingkai Xu
Superantigens can induce cell-mediated cytotoxicity preferentially against MHC II-positive target cells with large amounts of inflammatory cytokines releasing. In this study, superantigen staphylococcal enterotoxin C (SEC) 1 was investigated to evaluate its potential in bladder cancer immunotherapy in vitro and in vivo. Our results revealed that SEC1 could stimulate the proliferation of human peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner, accompanied with the release of interleukin-2, interferon-γ, and tumor necrosis factor-α, and increased the population of CD4(+) T cells and CD8(+) T cells...
July 17, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28715148/lineage-specific-epitope-profiles-for-hpai-h5-pre-pandemic-vaccine-selection-and-evaluation
#18
Xueting Qiu, Venkata R Duvvuri, Jonathan B Gubbay, Richard Webby, Ghazi Kayali, Justin Bahl
BACKGROUND: Multiple highly pathogenic avian influenza (HPAI) H5 viruses continue to co-circulate. This has complicated pandemic preparedness and confounded effective vaccine candidate selection and evaluation. OBJECTIVES: In this study we aim to predict and map the diversity of CD8+ T-cell epitopes among H5 Hemagglutinin (HA) gene lineages to estimate CD8+ T-cell immunity in humans induced by vaccine candidates. METHODS: A dataset consisting of 1125 H5 HA sequences collected between 1996 and 2017 from avian and humans was assembled for phylogenetic and lineage-specific epitope analyses...
July 17, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28714988/snp-mediated-disruption-of-ctcf-binding-at-the-ifitm3-promoter-is-associated-with-risk-of-severe-influenza-in-humans
#19
E Kaitlynn Allen, Adrienne G Randolph, Tushar Bhangale, Pranay Dogra, Maikke Ohlson, Christine M Oshansky, Anthony E Zamora, John P Shannon, David Finkelstein, Amy Dressen, John DeVincenzo, Miguela Caniza, Ben Youngblood, Carrie M Rosenberger, Paul G Thomas
Previous studies have reported associations of IFITM3 SNP rs12252 with severe influenza, but evidence of association and the mechanism by which risk is conferred remain controversial. We prioritized SNPs in IFITM3 on the basis of putative biological function and identified rs34481144 in the 5' UTR. We found evidence of a new association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity. We determined a role for rs34481144 as an expression quantitative trait locus (eQTL) for IFITM3, with the risk allele associated with lower mRNA expression...
July 17, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28714979/translation-is-actively-regulated-during-the-differentiation-of-cd8-effector-t-cells
#20
Koichi Araki, Masahiro Morita, Annelise G Bederman, Bogumila T Konieczny, Haydn T Kissick, Nahum Sonenberg, Rafi Ahmed
Translation is a critical process in protein synthesis, but translational regulation in antigen-specific T cells in vivo has not been well defined. Here we have characterized the translatome of virus-specific CD8(+) effector T cells (Teff cells) during acute infection of mice with lymphocytic choriomeningitis virus (LCMV). Antigen-specific T cells exerted dynamic translational control of gene expression that correlated with cell proliferation and stimulation via the T cell antigen receptor (TCR). The translation of mRNAs that encode translation machinery, including ribosomal proteins, was upregulated during the T cell clonal-expansion phase, followed by inhibition of the translation of those transcripts when the CD8(+) Teff cells stopped dividing just before the contraction phase...
July 17, 2017: Nature Immunology
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