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Virus specific t cells

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https://www.readbyqxmd.com/read/29684630/ligand-accessibility-to-the-hiv-1-env-co-receptor-binding-site-can-occur-prior-to-cd4-engagement-and-is-independent-of-viral-tier-category
#1
Saikat Boliar, Shilpa Patil, Brihaspati N Shukla, Ali Ghobbeh, Suprit Deshpande, Weizao Chen, Javier Guenaga, Dimiter S Dimitrov, Richard T Wyatt, Bimal K Chakrabarti
HIV-1 virus entry into target cells requires the envelope glycoprotein (Env) to first bind the primary receptor, CD4 and subsequently the co-receptor. Antibody access to the co-receptor binding site (CoRbs) in the pre-receptor-engaged state, prior to cell attachment, remains poorly understood. Here, we have demonstrated that for tier-1 Envs, the CoRbs is directly accessible to full-length CD4-induced (CD4i) antibodies even before primary receptor engagement, indicating that on these Envs the CoRbs site is either preformed or can conformationally sample post-CD4-bound state...
April 20, 2018: Virology
https://www.readbyqxmd.com/read/29684201/dysregulation-of-epstein-barr-virus-infection-in-hypomorphic-zap70-mutation
#2
Akihiro Hoshino, Takehiro Takashima, Kenichi Yoshida, Akira Morimoto, Yuta Kawahara, Tzu-Wen Yeh, Tsubasa Okano, Motoi Yamashita, Noriko Mitsuiki, Kohsuke Imai, Takashi Sakatani, Atsuko Nakazawa, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Tomohiro Morio, Hirokazu Kanegane
Background: Some patients with genetic defects develop Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD)/lymphoma as the main feature. Hypomophic mutations can cause different clinical and laboratory manifestations from null mutations in the same genes. Methods: We sought to describe the clinical and immunologic phenotype of a 21-month-old boy having EBV-associated LPD who was in good health till then. A genetic and immunologic analysis was performed...
April 19, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29681900/diverse-epitope-specificity-immunodominance-hierarchy-and-functional-avidity-of-effector-cd4-t-cells-established-during-priming-is-maintained-in-lung-after-influenza-a-virus-infection
#3
Katherine A Richards, Anthony T DiPiazza, Ajitanuj Rattan, Zackery A G Knowlden, Hongmei Yang, Andrea J Sant
One of the major contributions to protective immunity to influenza viruses that is provided by virus-specific CD4 T cells is delivery of effector function to the infected lung. However, there is little known about the selection and breadth of viral epitope-specific CD4 T cells that home to the lung after their initial priming. In this study, using a mouse model of influenza A infection and an unbiased method of epitope identification, the viral epitope-specific CD4 T cells elicited after infection were identified and quantified...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29677457/improved-protocol-for-simultaneous-analysis-of-leukocyte-subsets-and-epithelial-cells-from-murine-and-human-lung
#4
Christine Happle, Lena Meyer-Decking, Anika Dreier, Martin Wetzke, Stephanie Gläsener, Ruth Grychtol, Peter Braubach, Alexandra Jablonka, Sibylle Haid, Adan Chari Jirmo, Anika Habener, Jelena Skuljec, Gesine Hansen
PURPOSE: To study and isolate lung cells by flow cytometry, enzymatic digestion and generation of single cell suspensions is required. This significantly influences expression of cellular epitopes and protocols need to be adapted for the best isolation and subsequent analysis of specific cellular subsets. MATERIALS AND METHODS: We optimized protocols for the simultaneous isolation and characterization of specific human and murine lung cell types. For alveolar epithelial cells (AEC), a primarily dispase based digestion method and for leukocytes, a primarily collagenase based technique was adapted...
April 20, 2018: Experimental Lung Research
https://www.readbyqxmd.com/read/29675804/lactobacillus-plantarum-displaying-conserved-m2e-and-ha2-fusion-antigens-induces-protection-against-influenza-virus-challenge
#5
Wen-Tao Yang, Gui-Lian Yang, Liang Zhao, Yu-Bei Jin, Yan-Long Jiang, Hai-Bin Huang, Chun-Wei Shi, Jian-Zhong Wang, Guan Wang, Yuan-Huan Kang, Chun-Feng Wang
Avian influenza virus (AIV) can infect poultry, mammals, and other hosts and causes enormous economic losses to the global poultry industry. In this study, to develop a novel and potent oral vaccine based on Lactobacillus plantarum (L. plantarum) for controlling the spread of AIV in the poultry industry, we constructed a recombinant L. plantarum strain displaying the 3M2e-HA2 protein of the influenza virus and determined the effect of N/pgsA'-3M2e-HA2 against AIV in chicks. We first confirmed that the 3M2e-HA2 fusion protein was expressed on the surface of L...
April 19, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29673141/subunit-specific-role-of-nf-%C3%AE%C2%BAb-in-cancer
#6
REVIEW
Barbara Kaltschmidt, Johannes F W Greiner, Hussamadin M Kadhim, Christian Kaltschmidt
The transcription factor NF-κB is a key player in inflammation, cancer development, and progression. NF-κB stimulates cell proliferation, prevents apoptosis, and could promote tumor angiogenesis as well as metastasis. Extending the commonly accepted role of NF-κB in cancer formation and progression, different NF-κB subunits have been shown to be active and of particular importance in distinct types of cancer. Here, we summarize overexpression data of the NF-κB subunits RELA, RELB, and c-REL (referring to the v-REL, which is the oncogene of Reticuloendotheliosis virus strain T) as well as of their upstream kinase inhibitor, namely inhibitor of κB kinases (IKK), in different human cancers, assessed by database mining...
April 17, 2018: Biomedicines
https://www.readbyqxmd.com/read/29672707/longitudinal-study-of-cellular-and-systemic-cytokines-signatures-define-the-dynamics-of-a-balanced-immune-environment-in-disease-manifestation-in-zika-virus-infected-patients
#7
Fok-Moon Lum, David C B Lye, Jeslin J L Tan, Bernett Lee, Po-Ying Chia, Tze-Kwang Chua, Siti N Amrun, Yiu-Wing Kam, Wearn-Xin Yee, Wei-Ping Ling, Vanessa W X Lim, Vincent J X Pang, Linda K Lee, Esther W H Mok, Chia-Yin Chong, Yee-Sin Leo, Lisa F P Ng
Background: The unexpected re-emergence of Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Methods: Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex micro-bead assay, while changes in blood cell numbers were determined with immune-phenotyping...
April 16, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29672235/interleukin-7-regulates-t-follicular-helper-cell-function-in-patients-with-chronic-hepatitis-c
#8
Zhi-Hong Zhang, Ben-Chun Jiang, Xiao-Hong Liu, Meng-Xuan Zhang, Zhen-Sheng-Nan Li, Guang-Ze Zhu
Signaling through interleukin (IL)-7 is essential and required for development, differentiation, proliferation, and homeostasis of T cells. However, the role of IL-7 in regulation of CD4+ T cells in chronic viral infections was not fully elucidated. Thus, the aim of the current study was to investigate the immunomodulatory activity of IL-7 to T follicular helper (Tfh) cells and its contribution to pathogenesis of chronic HCV, hepatitis C virus (HCV) infection. A total of 47 patients with chronic hepatitis C and 19 normal controls were enrolled...
April 19, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29671786/hiv-vaccination-a-roadmap-among-advancements-and-concerns
#9
REVIEW
Maria Trovato, Luciana D'Apice, Antonella Prisco, Piergiuseppe De Berardinis
Since the identification of the Human Immunodeficiency Virus type 1 (HIV-1) as the etiologic agent of AIDS (Acquired Immunodeficiency Syndrome), many efforts have been made to stop the AIDS pandemic. A major success of medical research has been the development of the highly active antiretroviral therapy and its availability to an increasing number of people worldwide, with a considerable effect on survival. However, a safe and effective vaccine able to prevent and eradicate the HIV pandemic is still lacking...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29670617/restoration-of-decreased-t-helper-1-and-cd8-t-cell-subsets-is-associated-with-regression-of-lymphoproliferative-disorders-developed-during-methotrexate-treatment
#10
Shuntaro Saito, Katsuya Suzuki, Keiko Yoshimoto, Yuko Kaneko, Kunihiro Yamaoka, Takayuki Shimizu, Takehiko Mori, Shinichiro Okamoto, Kaori Kameyama, Koichi Amano, Jun-Ichi Tamaru, Michihide Tokuhira, Tsutomu Takeuchi
Background: Lymphoproliferative disorder (LPD), including malignant lymphoma, is a relatively rare but life-threatening complication in RA patients under methotrexate (MTX) therapy. Spontaneous regression of LPD after MTX withdrawal is regarded as a distinct characteristic in part of such LPDs. Objective: The present study aimed to investigate the immunological difference in regressive LPD and persistent LPD. Methods: We studied RA patients who developed LPD during MTX administration ( n  = 35) and clinically matched controls ( n  = 35)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29670614/human-v%C3%AE-9v%C3%AE-2-t-cells-synergize-cd4-t-follicular-helper-cells-to-produce-influenza-virus-specific-antibody
#11
Qingyun Chen, Kun Wen, Aizhen Lv, Ming Liu, Ke Ni, Zheng Xiang, Yinping Liu, Wenwei Tu
Human Vγ9Vδ2-T cells recognize nonpeptidic antigens and exert effector functions against microorganisms and tumors, but little is known about their roles in humoral immune response against influenza virus infection. Herein, in the coculture of autologous human B cells, dendritic cells and/or naïve CD4 T cells, and Vγ9Vδ2-T cells, we demonstrated that Vγ9Vδ2-T cells could facilitate H9N2 influenza virus-specific IgG and IgM productions in a CD4 T cell-dependent manner. Vγ9Vδ2-T cells promoted the differentiation of CXCR5+ PD1+ CD4+ T follicular helper (Tfh) cells, CD19+ IgD- CD38++ plasma cells (PCs), and drove B cell proliferation as well as immunoglobulin class switching...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669837/amino-acid-substitutions-within-hla-b-27-restricted-t-cell-epitopes-prevent-recognition-by-hepatitis-delta-virus-specific-cd8-t-cells
#12
Hadi Karimzadeh, Muthamia M Kiraithe, Anna D Kosinska, Manuel Glaser, Melanie Fiedler, Valerie Oberhardt, Elahe Salimi Alizei, Maike Hofmann, Juk Yee Mok, Melanie Nguyen, Wim J E van Esch, Bettina Budeus, Jan Grabowski, Maria Homs, Antonella Olivero, Hossein Keyvani, Francisco Rodríguez-Frías, David Tabernero, Maria Buti, Andreas Heinold, Seyed Moayed Alavian, Tanja Bauer, Julian Schulze Zur Wiesch, Bijan Raziorrouh, Daniel Hoffmann, Antonina Smedile, Mario Rizzetto, Heiner Wedemeyer, Jörg Timm, Iris Antes, Christoph Neumann-Haefelin, Ulrike Protzer, Michael Roggendorf
Virus-specific CD8 T-cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T-cell epitope repertoire and mechanisms of CD8 T-cell failure in HDV infection have merely been characterized. We therefore aimed to characterize HDV-specific CD8 T cell epitopes and the impact of viral mutations on immune escape. In this study, we predicted peptide epitopes binding the most frequent HLA types and assessed their HLA binding capacity. These epitopes were characterized in HDV-infected patients by intracellular IFN-γ staining...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29669836/cd4-t-cell-epitope-specificity-and-cytokine-potential-are-preserved-as-cells-transition-from-the-lung-vasculature-to-lung-tissue-following-influenza-infection
#13
Anthony DiPiazza, Nathan Laniewski, Anuj Rattan, David J Topham, Jim Miller, Andrea J Sant
Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza infection in conjunction with intravascular labeling in vivo , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29669829/incomplete-downregulation-of-cd4-expression-affects-hiv-1-env-conformation-and-adcc-responses
#14
Jérémie Prévost, Jonathan Richard, Halima Medjahed, Audrey Alexander, Jennifer Jones, John C Kappes, Christina Ochsenbauer, Andrés Finzi
HIV-1 infected cells expressing envelope glycoproteins (Env) in the CD4-bound conformation on their surface are targeted by antibody-dependent cellular cytotoxicity (ADCC) mediated by CD4-induced (CD4i) antibodies and HIV+ sera. By downregulating the surface expression of CD4, Nef prevents Env-CD4 interaction thus protecting HIV-1-infected cells from ADCC. HIV-1 infectious molecular clones (IMC) are widely used to measure ADCC. In order to facilitate the identification of infected cells and high-throughput ADCC analysis, reporter genes (e...
April 18, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29669806/targeting-merkel-cell-carcinoma-by-engineered-t-cells-specific-to-t-antigens-of-merkel-cell-polyomavirus
#15
Ioannis Gavvovidis, Matthias Leisegang, Gerald Willimsky, Natalie J Miller, Paul Nghiem, Thomas Blankenstein
PURPOSE: The causative agent of most cases of Merkel cell carcinoma (MCC) has been identified as the Merkel cell polyomavirus (MCV). MCV-encoded T-antigens (Tags) are essential not only for virus-mediated tumorigenesis but also for maintaining MCC cell lines in vitro. MCV Tags are thus an appealing target for viral oncoprotein-directed T cell therapy for MCC. With this study, we aimed to isolate and characterize Tag-specific T cell receptors (TCR) for potential use in gene therapy clinical trials...
April 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29669782/the-respiratory-environment-diverts-the-development-of-antiviral-memory-cd8-t-cells
#16
Hillary L Shane, Katie L Reagin, Kimberly D Klonowski
Our understanding of memory CD8+ T cells has been largely derived from acute, systemic infection models. However, memory CD8+ T cells generated from mucosal infection exhibit unique properties and, following respiratory infection, are not maintained in the lung long term. To better understand how infection route modifies memory differentiation, we compared murine CD8+ T cell responses to a vesicular stomatitis virus (VSV) challenge generated intranasally (i.n.) or i.v. The i.n. infection resulted in greater peak expansion of VSV-specific CD8+ T cells...
April 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29668327/assessment-of-humoral-innate-and-t-cell-immune-responses-to-adeno-associated-virus-vectors
#17
Roberto Calcedo, Jessica A Chichester, James M Wilson
Adeno-associated virus (AAV)-based gene therapy is being applied to treat a wide array of diseases. Preexisting host immune responses to AAV and immune responses elicited by AAV vector administration remain a problem that needs to be further studied. Here we present a series of protocols to assess immune responses before and after AAV vector administration that are applicable to multiple animal models and phase 1 clinical trials. More specifically, they may be use to evaluate (1) the humoral immune response, through levels of AAV-neutralizing and binding antibodies; (2) the innate immune response, through the acute induction of inflammatory cytokines; and (3) the T-cell immune response, through the activation of transgene- and vector-specific CD8+ and CD4+ T cells...
April 2018: Human Gene Therapy Methods
https://www.readbyqxmd.com/read/29666167/a-flexible-mhc-class-i-multimer-loading-system-for-large-scale-detection-of-antigen-specific-t-cells
#18
Jolien J Luimstra, Malgorzata A Garstka, Marthe C J Roex, Anke Redeker, George M C Janssen, Peter A van Veelen, Ramon Arens, J H Frederik Falkenburg, Jacques Neefjes, Huib Ovaa
Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2Kb that form stable peptide-MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature...
April 17, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29665376/insect-cell-produced-recombinant-protein-subunit-vaccines-protect-against-zika-virus-infection
#19
Panke Qu, Wei Zhang, Dapeng Li, Chao Zhang, Qingwei Liu, Xueyang Zhang, Xuesong Wang, Wenlong Dai, Yongfen Xu, Qibin Leng, Jin Zhong, Xia Jin, Zhong Huang
Infection with Zika virus (ZIKV) may lead to severe neurologic disorders. It is of significant importance and urgency to develop safe and effective vaccines to prevent ZIKV infection. Here we report the development of ZIKV subunit vaccines based on insect cell-produced recombinant proteins. The N-terminal approximately 80% region (designated as E80) and the domain III (designated as EDIII) of ZIKV envelope (E) protein were efficiently produced as secreted proteins in a Drosophila S2 cell expression system. Both E80 and EDIII could inhibit ZIKV infection in vitro, suggesting that they may have folded properly to display native conformations...
April 14, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29664577/the-gradual-rise-of-memory-inflation
#20
REVIEW
Paul Klenerman
Memory inflation, as a term, has been used for 15 years now to describe the longitudinal development of stable, expanded CD8+ T memory pools with a distinct phenotype and functional profile which emerge in specific infection and vaccine settings. These settings have in common the persistence of antigen, especially cytomegalovirus infection but also more recently adenoviral vector vaccination. However, in contrast to chronic infections which lead to "exhaustion" the repeated antigen encounters experienced by CD8+ T cells lead to development of a robust T-cell population structure which maintains functionality and size...
May 2018: Immunological Reviews
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