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https://www.readbyqxmd.com/read/29474461/distinct-susceptibility-of-hiv-vaccine-vector-induced-cd4-t-cells-to-hiv-infection
#1
Sarah Auclair, Fengliang Liu, Qingli Niu, Wei Hou, Gavin Churchyard, Cecilia Morgan, Nicole Frahm, Sorachai Nitayaphan, Punnee Pitisuthithum, Supachai Rerks-Ngarm, Jason T Kimata, Lynn Soong, Genoveffa Franchini, Merlin Robb, Jerome Kim, Nelson Michael, Haitao Hu
The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial...
February 23, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29474450/treatment-with-native-heterodimeric-il-15-increases-cytotoxic-lymphocytes-and-reduces-shiv-rna-in-lymph-nodes
#2
Dionysios C Watson, Eirini Moysi, Antonio Valentin, Cristina Bergamaschi, Santhi Devasundaram, Sotirios P Fortis, Jenifer Bear, Elena Chertova, Julian Bess, Ray Sowder, David J Venzon, Claire Deleage, Jacob D Estes, Jeffrey D Lifson, Constantinos Petrovas, Barbara K Felber, George N Pavlakis
B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29474442/dysregulation-of-the-ifn-%C3%AE-stat1-signaling-pathway-in-a-cell-line-model-of-large-granular-lymphocyte-leukemia
#3
Paige M Kulling, Kristine C Olson, Cait E Hamele, Mariella F Toro, Su-Fern Tan, David J Feith, Thomas P Loughran
T cell large granular lymphocyte leukemia (T-LGLL) is a rare incurable disease that is characterized by defective apoptosis of cytotoxic CD8+ T cells. Chronic activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is a hallmark of T-LGLL. One manifestation is the constitutive phosphorylation of tyrosine 701 of STAT1 (p-STAT1). T-LGLL patients also exhibit elevated serum levels of the STAT1 activator, interferon-γ (IFN-γ), thus contributing to an inflammatory environment...
2018: PloS One
https://www.readbyqxmd.com/read/29472932/-in-vitro-generated-tc17-cells-present-a-memory-phenotype-and-serve-as-a-reservoir-of-tc1-cells-in-vivo
#4
Felipe Flores-Santibáñez, Bárbara Cuadra, Dominique Fernández, Mariana V Rosemblatt, Sarah Núñez, Pablo Cruz, Felipe Gálvez-Cancino, J César Cárdenas, Alvaro Lladser, Mario Rosemblatt, María Rosa Bono, Daniela Sauma
Memory CD8+ T cells are ideal candidates for cancer immunotherapy because they can mediate long-term protection against tumors. However, the therapeutic potential of different in vitro -generated CD8+ T cell effector subsets to persist and become memory cells has not been fully characterized. Type 1 CD8+ T (Tc1) cells produce interferon-γ and are endowed with high cytotoxic capacity, whereas IL-17-producing CD8+ T (Tc17) cells are less cytotoxic but display enhanced self-renewal capacity. We sought to evaluate the functional properties of in vitro -generated Tc17 cells and elucidate their potential to become long lasting memory cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29472931/dendritic-cell-migration-to-skin-draining-lymph-nodes-is-controlled-by-dermatan-sulfate-and-determines-adaptive-immunity-magnitude
#5
Reza Nadafi, Jasper J Koning, Henrike Veninga, Xanthi N Stachtea, Tanja Konijn, Antonie Zwiers, Anders Malmström, Joke M M den Haan, Reina E Mebius, Marco Maccarana, Rogier M Reijmers
For full activation of naïve adaptive lymphocytes in skin-draining lymph nodes (LNs), presentation of peptide:MHC complexes by LN-resident and skin-derived dendritic cells (DCs) that encountered antigens (Ags) is an absolute prerequisite. To get to the nearest draining LN upon intradermal immunization, DCs need to migrate from the infection site to the afferent lymphatics, which can only be reached by traversing a collagen-dense network located in the dermis of the skin through the activity of proteolytic enzymes...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29472929/infectious-sporozoites-of-plasmodium-berghei-effectively-activate-liver-cd8%C3%AE-dendritic-cells
#6
Rajesh Parmar, Hardik Patel, Naveen Yadav, Ritika Parikh, Khyati Patel, Aditi Mohankrishnan, Vishakha Bhurani, Urja Joshi, Sarat Kumar Dalai
Immunization with radiation-attenuated sporozoites (RAS) shown to confer complete sterile protection against Plasmodia liver-stage (LS) infection that lasts about 6 to 9 months in mice. We have found that the intermittent infectious sporozoite challenge to immune mice following RAS vaccination extends the longevity of sterile protection by maintaining CD8+ T cell memory responses to LS infection. It is reported that CD8α+ dendritic cells (DCs) are involved in the induction of LS-specific CD8+ T cells following RAS or genetically attenuated parasite (GAP) vaccination...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29472924/signal-transducer-and-activator-of-transcription-3-control-of-human-t-and-b-cell-responses
#7
REVIEW
Elissa K Deenick, Simon J Pelham, Alisa Kane, Cindy S Ma
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated downstream of many key cytokine receptors expressed by lymphocytes. As such, it plays a critical role in regulating B cells as well as CD4+ and CD8+ T cells. Patients with clinically significant immunodeficiency and immune dysregulation resulting from loss-of-function or gain-of-function mutations in STAT3 have been described. These individuals provide insight into the critical role of this transcription factor in the regulation of immune responses and the balance between effective immune protection and autoimmunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29472720/car-t-cells-targeting-flt3-have-potent-activity-against-flt3-itd-aml-and-act-synergistically-with-the-flt3-inhibitor-crenolanib
#8
Hardikkumar Jetani, Irene Garcia-Cadenas, Thomas Nerreter, Simone Thomas, Julian Rydzek, Javier Briones Meijide, Halvard Bonig, Wolfgang Herr, Jordi Sierra, Hermann Einsele, Michael Hudecek
FMS-like tyrosine kinase 3 (FLT3) is a transmembrane protein expressed on normal hematopoietic stem and progenitor cells (HSC) and retained on malignant blasts in acute myeloid leukemia (AML). We engineered CD8+ and CD4+ T-cells expressing a FLT3-specific chimeric antigen receptor (CAR) and demonstrate they confer potent reactivity against AML cell lines and primary AML blasts that express either wild-type FLT3 or FLT3 with internal tandem duplication (FLT3-ITD). We also show that treatment with the FLT3-inhibitor crenolanib leads to increased surface expression of FLT3 specifically on FLT3-ITD+ AML cells and consecutively, enhanced recognition by FLT3-CAR T-cells in vitro and in vivo...
February 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29472691/a-reappraisal-of-ctla-4-checkpoint-blockade-in-cancer-immunotherapy
#9
Xuexiang Du, Fei Tang, Mingyue Liu, Juanjuan Su, Yan Zhang, Wei Wu, Martin Devenport, Christopher A Lazarski, Peng Zhang, Xu Wang, Peiying Ye, Changyu Wang, Eugene Hwang, Tinghui Zhu, Ting Xu, Pan Zheng, Yang Liu
It is assumed that anti-CTLA-4 antibodies cause tumor rejection by blocking negative signaling from B7-CTLA-4 interactions. Surprisingly, at concentrations considerably higher than plasma levels achieved by clinically effective dosing, the anti-CTLA-4 antibody Ipilimumab blocks neither B7 trans-endocytosis by CTLA-4 nor CTLA-4 binding to immobilized or cell-associated B7. Consequently, Ipilimumab does not increase B7 on dendritic cells (DCs) from either CTLA4 gene humanized (Ctla4h/h ) or human CD34+ stem cell-reconstituted NSG™ mice...
February 22, 2018: Cell Research
https://www.readbyqxmd.com/read/29472563/non-invasive-radiofrequency-field-treatment-of-4t1-breast-tumors-induces-t-cell-dependent-inflammatory-response
#10
Jared M Newton, Jose H Flores-Arredondo, Sarah Suki, Matthew J Ware, Martyna Krzykawska-Serda, Mahdi Agha, Justin J Law, Andrew G Sikora, Steven A Curley, Stuart J Corr
Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29472446/hematopoiesis-by-ipsc-derived-hematopoietic-stem-cells-of-aplastic-anemia-that-escape-cytotoxic-t-cell-attack
#11
J Luis Espinoza, Mahmoud I Elbadry, Kazuhisa Chonabayashi, Yoshinori Yoshida, Takamasa Katagiri, Kenichi Harada, Noriharu Nakagawa, Yoshitaka Zaimoku, Tatsuya Imi, Hassan A Hassanein, Amal Khalifa A Noreldin, Katsuto Takenaka, Koichi Akashi, Hiroshi Hamana, Hiroyuki Kishi, Yoshiki Akatsuka, Shinji Nakao
Hematopoietic stem cells (HSCs) that lack HLA-class I alleles as a result of copy-number neutral loss of heterozygosity of the short arm of chromosome 6 (6pLOH) or HLA allelic mutations often constitute hematopoiesis in patients with acquired aplastic anemia (AA), but the precise mechanisms underlying clonal hematopoiesis induced by these HLA-lacking (HLA- ) HSCs remain unknown. To address this issue, we generated induced pluripotent stem cells (iPSCs) from an AA patient who possessed HLA - B4002-lacking (B4002- ) leukocytes...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29472350/memory-cd8-t-cells-support-the-maintenance-of-hematopoietic-stem-cells-in-the-bone-marrow
#12
Sulima Geerman, Giso Brasser, Sudeep Bhushal, Fiamma Salerno, Natasja A Kragten, Mark Hoogenboezem, Gerald de Haan, Monika C Wolkers, María Fernanda Pascutti, Martijn A Nolte
No abstract text is available yet for this article.
February 22, 2018: Haematologica
https://www.readbyqxmd.com/read/29472249/improved-murine-mhc-deficient-hla-transgenic-nod-mouse-models-for-type-1-diabetes-therapy-development
#13
Jeremy J Racine, Isabel Stewart, Jeremy Ratiu, Greg Christianson, Emily Lowell, Kelsay Helm, Jennifer Allocco, Richard S Maser, Yi-Guang Chen, Cathleen M Lutz, Derry Roopenian, Jennifer Schloss, Teresa P DiLorenzo, David V Serreze
Improved mouse models for type 1 diabetes (T1D) therapy development are needed. T1D susceptibility is restored to normally resistant NOD.β2m-/- mice transgenically expressing human disease associated HLA-A*02:01 or HLA-B*39:06 class I molecules in place of their murine counterparts. T1D is dependent on pathogenic CD8+ T-cell responses mediated by these human class I variants. NOD.β2m-/- -A2.1 mice were previously used to identify β-cell autoantigens presented by this human class I variant to pathogenic CD8+ T-cells, and for testing therapies to attenuate such effectors...
February 22, 2018: Diabetes
https://www.readbyqxmd.com/read/29472141/t-cell-deficiencies-as-a-common-risk-factor-for-drug-associated-progressive-multifocal-leukoencephalopathy
#14
REVIEW
Dejan Pavlovic, Mayur A Patel, Andriani C Patera, Ilse Peterson
Progressive multifocal leukoencephalopathy (PML) is a disease of the central nervous system caused by neuropathogenic prototypes of ubiquitous community-acquired JC virus (JCV). The disease became of particular concern following its association with certain therapies that modulate immune system function without heavy immunosuppression. Due to lack of prophylactic/treatment options and poor outcomes, which often include severe disability or death, PML is a considerable concern for development of new drugs that interfere with immune system functions...
February 2, 2018: Immunobiology
https://www.readbyqxmd.com/read/29471808/whole-genome-duplications-have-provided-teleosts-with-many-roads-to-peptide-loaded-mhc-class-i-molecules
#15
Unni Grimholt
BACKGROUND: In sharks, chickens, rats, frogs, medaka and zebrafish there is haplotypic variation in MHC class I and closely linked genes involved in antigen processing, peptide translocation and peptide loading. At least in chicken, such MHCIa haplotypes of MHCIa, TAP2 and Tapasin are shown to influence the repertoire of pathogen epitopes being presented to CD8+ T-cells with subsequent effect on cell-mediated immune responses. RESULTS: Examining MHCI haplotype variation in Atlantic salmon using transcriptome and genome resources we found little evidence for polymorphism in antigen processing genes closely linked to the classical MHCIa genes...
February 23, 2018: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/29471676/results-and-challenges-of-immune-checkpoint-inhibitors-in-colorectal-cancer
#16
Sheik Emambux, Gaelle Tachon, Audelaure Junca, David Tougeron
Introduction Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and clinical outcome has improved substantially during the last two decades with targeted therapies. The immune system has a major role in cancers, especially the CD8+ T cells specific to tumor antigens. However, tumors can escape immune response by different mechanisms including upregulation of inhibitory immune checkpoint receptors, such as well-known Programmed cell Death protein-1 (PD-1)/Programmed cell Death Ligand 1 (PD-L1) interaction, leading CD8+ T cells to a state of anergy...
February 22, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29471387/heavy-cannabis-use-associated-with-reduction-in-activated-and-inflammatory-immune-cell-frequencies-in-antiretroviral-therapy-treated-human-immunodeficiency-virus-infected-individuals
#17
Jennifer A Manuzak, Toni M Gott, Jay S Kirkwood, Ernesto Coronado, Tiffany Hensley-McBain, Charlene Miller, Ryan K Cheu, Ann C Collier, Nicholas T Funderburg, Jeffery N Martin, Michael C Wu, Nina Isoherranen, Peter W Hunt, Nichole R Klatt
Background: Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)-infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined. Methods: The impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry...
February 17, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29469316/-clinical-features-of-imported-schistosomiasis-mansoni-in-beijing-city%C3%AF-a-report-of-6-cases
#18
Zou Yang, Wang Lei, Li Xiao-Li, Tian Xiao-Jun, Li Wei, An Yi-Jun, Qi Zhi-Qun, Li Jing-Jing, Wang Fei, Huang Min-Jun
OBJECTIVE: To analyze the clinical features of 6 patients with imported schistosomiasis mansoni, including the epidemic history, clinical manifestations, laboratory tests and therapeutic effect, so as to provide references for improving the levels of diagnosis and treatment of physicians. METHODS: The clinical data of 6 patients with imported schistosomiasis mansoni from January 2009 to July 2016 were collected and analyzed. RESULTS: All the 6 imported patients with schistosomiasis mansoni had a clear history of cercarial infested water exposure...
March 10, 2017: Zhongguo Xue Xi Chong Bing Fang Zhi za Zhi, Chinese Journal of Schistosomiasis Control
https://www.readbyqxmd.com/read/29469044/tcr-v%C3%AE-usage-of-peripheral-blood-and-liver-infiltrating-lymphocytes-in-patients-with-chronic-hepatitis-b
#19
Jianwei Zhou, Cui Kong, Bo Ban, Haixin Dong, Chengqiang Jin
INTRODUCTION: Chronic hepatitis B (CHB) is still a public health problem and its mechanism remains unclear. In this study, we detect the skewness of T cell receptor beta chain variable gene (TCR Vβ) in peripheral blood lymphocytes (PBL) and the liver infiltrating lymphocytes (LIL) of patients with CHB; and hope to provide information for further research on the pathogenic mechanism of CHB. MATERIAL AND METHODS: Fifteen patients with CHB, ten healthy volunteers and three patients with liver cysts were recruited as the subjects...
March 1, 2018: Annals of Hepatology
https://www.readbyqxmd.com/read/29468827/exploration-of-antigen-induced-caco-3-nanoparticles-for-therapeutic-vaccine
#20
Shuang Wang, Dezhi Ni, Hua Yue, Nana Luo, Xiaobo Xi, Yugang Wang, Min Shi, Wei Wei, Guanghui Ma
Therapeutic vaccines possess particular advantages and show promising potential to combat burdening diseases, such as acquired immunodeficiency syndrome, hepatitis, and even cancers. An efficient therapeutic vaccine would strengthen the immune system and eventually eliminate target cells through cytotoxic T lymphocytes (CTLs). Unfortunately, insufficient efficacy in triggering such an adaptive immune response is a problem that remains unsolved. To achieve efficient cellular immunity, antigen-presenting cells must capture and further cross-present disease-associated antigens to CD8 T cells via major histocompatibility complex I molecules...
February 22, 2018: Small
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