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https://www.readbyqxmd.com/read/28635557/cellular-immune-responses-of-older-adults-to-four-influenza-vaccines-results-of-a-randomized-controlled-comparison
#1
Arun Kumar, Janet E McElhaney, Lisa Walrond, Terry D Cyr, Shahzma Merani, Tobias R Kollmann, Scott A Halperin, David W Scheifele
Cellular immunity is important for protection against the serious complications of influenza in older adults. As it is unclear if newer influenza vaccines elicit greater cellular responses than standard vaccines, we compared responses to two standard and two newer licensed trivalent inactivated vaccines (TIVs) in a randomized trial in older adults. Non-frail adults ≥65 years old were randomly assigned to receive standard subunit, MF59-adjuvanted subunit, standard split-virus or intradermal split-virus TIV...
June 21, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28631177/trail-in-cd8-t-cells-from-patients-with-severe-aplastic-anemia
#2
Chunyan Liu, Mengying Zheng, Tian Zhang, Rong Fu, Huaquan Wang, Ting Wang, Weiwei Qi, Zonghong Shao
Severe aplastic anemia (SAA) is an autoimmune disease caused mainly by activated T lymphocytes. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of TNF family, which can induce apoptosis and play a significant role in the pathogenesis of many autoimmune disorders. In this study, we sought to investigate the role of TRAIL in peripheral CD8+ T cells (CTLs) from SAA patients to clarify the autoimmune mechanisms of bone marrow failure in SAA. The expression of TRAIL and TRAIL-R2 in CTLs from SAA patients and normal controls were determined by flow cytometry, real-time PCR, and western blot...
June 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28630152/repurposing-a-pore-highly-conserved-perforin-like-proteins-with-alternative-mechanisms
#3
REVIEW
Tao Ni, Robert J C Gilbert
Pore-forming proteins play critical roles in pathogenic attack and immunological defence. The membrane attack complex/perforin (MACPF) group of homologues represents, with cholesterol-dependent cytolysins, the largest family of such proteins. In this review, we begin by describing briefly the structure of MACPF proteins, outlining their common mechanism of pore formation. We subsequently discuss some examples of MACPF proteins likely implicated in pore formation or other membrane-remodelling processes. Finally, we focus on astrotactin and bone morphogenetic protein and retinoic acid-induced neural-specific proteins, highly conserved MACPF family members involved in developmental processes, which have not been well studied to date or observed to form a pore-and which data suggest may act by alternative mechanisms...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28616288/decreased-expression-of-perforin-in-cd8-t-lymphocytes-in-patients-with-mycobacterium-tuberculosis-infection-and-its-potential-value-as-a-marker-for-efficacy-of-treatment
#4
Hongbin Jiang, Huili Gong, Qing Zhang, Jin Gu, Li Liang, Jun Zhang
BACKGROUND: Cytolytic activity against mycobacteria tuberculosis (MTB) within the infected macrophage is a crucial step in the immunity against TB infection, as MTB is an intracellular bacterium. Cytotoxic molecules such as perforin and granzymes produced by cytolytic T cells directly participate in this process. In this study, we evaluated the cytotoxicity function employing flow cytometry analysis of the level of expression of interferon-γ (IFN-γ), perforin and granzyme B in CD8(+) T cells from patients with active pulmonary TB (PTB), stable PTB and healthy controls, and explored whether MTB antigen (MTB Ag)-stimulated cytotoxic molecules would be useful for monitoring responses to anti-TB treatment...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28603092/crosstalk-of-liver-immune-cells-and-cell-death-mechanisms-in-different-murine-models-of-liver-injury-and-its-clinical-relevance
#5
Hilal Ahmad Khan, Muhammad Zishan Ahmad, Junaid Ali Khan, Muhammad Imran Arshad
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions...
June 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28582670/substituted-arylsulphonamides-as-inhibitors-of-perforin-mediated-lysis
#6
Julie A Spicer, Christian K Miller, Patrick D O'Connor, Jiney Jose, Kristiina M Huttunen, Jagdish K Jaiswal, William A Denny, Hedieh Akhlaghi, Kylie A Browne, Joseph A Trapani
The structure-activity relationships for a series of arylsulphonamide-based inhibitors of the pore-forming protein perforin have been explored. Perforin is a key component of the human immune response, however inappropriate activity has also been implicated in certain auto-immune and therapy-induced conditions such as allograft rejection and graft versus host disease. Since perforin is expressed exclusively by cells of the immune system, inhibition of this protein would be a highly selective strategy for the immunosuppressive treatment of these disorders...
May 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28579805/bisdemethoxycurcumin-in-combination-with-%C3%AE-pd-l1-antibody-boosts-immune-response-against-bladder-cancer
#7
Yiqun Shao, Wenjing Zhu, Jun Da, Mingxi Xu, Yiwei Wang, Juan Zhou, Zhong Wang
Curcumin was recently discovered to strengthen immune response through multiple mechanisms. Cytotoxic CD8(+) T-cells play a critical role in modulating anticancer immune response, but is severely restricted by T-cell exhaustion. Bladder carcinomas express PD-L1 and can abrogate CD8(+) T-cell response. Thus, we hypothesized that bisdemethoxycurcumin, a natural dimethoxy derivative of curcumin, may provide a favorable environment for T-cell response against bladder cancer when used in combination with α-PD-L1 antibody...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28578124/influence-of-photodynamic-therapy-on-peripheral-immune-cell-populations-and-cytokine-concentrations-in-head-and-neck-cancer
#8
M N Theodoraki, K Lorenz, R Lotfi, D Fürst, C Tsamadou, S Jaekle, J Mytilineos, C Brunner, J Theodorakis, T K Hoffmann, S Laban, P J Schuler
BACKGROUND: Photodynamic therapy (PDT) represents a palliative treatment option for a selected group of patients with head and neck squamous cell carcinoma (HNSCC). PDT induces a local inflammatory reaction with the potential to initiate antitumor immune responses. However, the systemic impact on peripheral immune cells has not been described so far. METHODS: HNSCC patients (n=9) were treated with PDT in a palliative setting. All patients had previously undergone several oncologic treatment regimens...
May 31, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28577134/role-of-oxidative-stress-in-the-suppression-of-immune-responses-in-peripheral-blood-mononuclear-cells-exposed-to-combustible-tobacco-product-preparation
#9
Subhashini Arimilli, Eckhardt Schmidt, Brad E Damratoski, G L Prasad
Cigarette smoking is a major risk factor for several human diseases. Chronic inflammation, resulting from increased oxidative stress, has been suggested as a mechanism that contributes to the increased susceptibility of smokers to cancer and microbial infections. We have previously shown that whole-smoke conditioned medium (WS-CM) and total particulate matter (TPM) prepared from Kentucky 3R4F reference cigarettes [collectively called as combustible tobacco product preparations (TPPs)] potently suppressed agonist-stimulated cytokine secretion and target cell killing in peripheral blood mononuclear cells (PBMCs)...
June 2, 2017: Inflammation
https://www.readbyqxmd.com/read/28572174/go-with-the-flow-perforin-and-cd107a-in-hlh
#10
Melissa R Hines, Kim E Nichols
No abstract text is available yet for this article.
June 1, 2017: Blood
https://www.readbyqxmd.com/read/28559404/peripheral-t-cell-reactivity-to-heat-shock-protein-70-and-its-cofactor-grpe-from-tropheryma-whipplei-is-reduced-in-patients-with-classical-whipple-s-disease
#11
Lucia Trotta, Kathleen Weigt, Katina Schinnerling, Anika Geelhaar-Karsch, Gerrit Oelkers, Federico Biagi, Gino Roberto Corazza, Kristina Allers, Thomas Schneider, Ulrike Erben, Verena Moos
Background: Classical Whipple's disease (CWD) is characterized by the lack of specific Th1 response towards Tropheryma (T.) whipplei in genetically predisposed individuals. The cofactor GrpE of heat-shock protein 70 (Hsp70) from T. whipplei was previously identified as B-cell antigen. We tested the capacity of Hsp70 and GrpE to elicit specific pro-inflammatory T-cell responses.Methods: Peripheral mononuclear cells from CWD patients and healthy donors were stimulated with T. whipplei lysate or recombinant GrpE or Hsp70 before CD40L, CD69, perforin, granzyme B, CD107a, and interferon (IFN)γ were determined in T cells by flow cytometry...
May 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28549488/microwave-induced-apoptosis-and-cytotoxicity-of-nk-cells-through-erk1-2-signaling
#12
Li Zhao, Jing Li, Yan Hui Hao, Ya Bing Gao, Shui Ming Wang, Jing Zhang, Ji Dong, Hong Mei Zhou, Shu Chen Liu, Rui Yun Peng
OBJECTIVE: To investigate microwave-induced morphological and functional injury of natural killer (NK) cells and uncover their mechanisms. METHODS: NK-92 cells were exposed to 10, 30, and 50 mW/cm2 microwaves for 5 min. Ultrastructural changes, cellular apoptosis and cell cycle regulation were detected at 1 h and 24 h after exposure. Cytotoxic activity was assayed at 1 h after exposure, while perforin and NKG2D expression were detected at 1 h, 6 h, and 12 h after exposure...
May 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28546503/frontline-science-functionally-impaired-geriatric-car-t-cells-rescued-by-increased-%C3%AE-5%C3%AE-1-integrin-expression
#13
Prajna Guha, Marissa Cunetta, Ponnandai Somasundar, N Joseph Espat, Richard P Junghans, Steven C Katz
Chimeric antigen receptor expressing T cells (CAR-T) are a promising form of immunotherapy, but the influence of age-related immune changes on CAR-T production remains poorly understood. We showed that CAR-T cells from geriatric donors (gCAR-T) are functionally impaired relative to CAR-T from younger donors (yCAR-T). Higher transduction efficiencies and improved cell expansion were observed in yCAR-T cells compared with gCAR-T. yCAR-T demonstrated significantly increased levels of proliferation and signaling activation of phosphorylated (p)Erk, pAkt, pStat3, and pStat5...
May 25, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28537251/antigen-specific-cd8-t-cell-feedback-activates-nlrp3-inflammasome-in-antigen-presenting-cells-through-perforin
#14
Yikun Yao, Siyuan Chen, Mengtao Cao, Xing Fan, Tao Yang, Yin Huang, Xinyang Song, Yongqin Li, Lilin Ye, Nan Shen, Yufang Shi, Xiaoxia Li, Feng Wang, Youcun Qian
The connection between innate and adaptive immunity is best exemplified by antigen presentation. Although antigen-presenting cells (APCs) are required for antigen receptor-mediated T-cell activation, how T-cells feedback to APCs to sustain an antigen-specific immune response is not completely clear. Here we show that CD8(+) T-cell (also called cytotoxic T lymphocytes, CTL) feedback activates the NLRP3 inflammasome in APCs in an antigen-dependent manner to promote IL-1β maturation. Perforin from antigen-specific CTLs is required for NLRP3 inflammasome activation in APCs...
May 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28530155/an-oncolytic-adenovirus-encoding-decorin-and-gm-csf-inhibits-tumor-growth-in-a-colorectal-tumor-model-by-targeting-pro-tumorigenic-signals-and-via-immune-activation
#15
Zhao Liu, Yuefeng Yang, Xiaoyan Zhang, Hao Wang, Weidong Xu, Hua Wang, FengJun Xiao, Zhigang Bai, Hongwei Yao, Xuemei Ma, Lan Jin, Chu-Tse Wu, Prem Seth, Zhongtao Zhang, Lisheng Wang
In advanced and metastatic stages of colorectal cancer (CRC), reduced sensitivity to conventional strategies is still a major obstacle to successful treatments. Decorin is an important regulator in the development and progression of various cancers. To examine if CRC patients have altered decorin levels, expression of decorin and its target genes, Met and vascular endothelial growth factor A (VEGFA) were analyzed in their tumors. Compared to normal tissues, decorin expression was reduced in CRC patients' tumors, while, there were increased Met and VEGFA levels...
May 20, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28529568/a-different-representation-of-natural-t-cells-and-natural-killer-cells-between-tumor-infiltrating-and-periphery-lymphocytes-in-human-hepatocellular-carcinoma
#16
Xiao-Feng Li, Dong Dai, Xiu-Yu Song, Jian-Jing Liu, Lei Zhu, Xiang Zhu, Wenchao Ma, Wengui Xu
Natural T cells [cluster of differentiation (CD) 3(+)CD56(+)] and natural killer (NK) cells (CD3(-)CD56(+)) are particularly abundant in the human liver and serve an important role in immune responses in the liver. The aim of the present study was to extensively determine the phenotypic and functional characteristics of natural T and NK cells in human hepatocellular carcinoma (HCC). Tumorous and non-tumorous tissue infiltrating lymphocytes (TILs and NILs, respectively) and peripheral blood mononuclear cells (PBMCs) from patients with hepatocellular carcinoma (HCC) were obtained to determine the frequency and phenotype of natural T/NK cells by a multicolor fluorescence activated cell sorting analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28507795/digital-analysis-and-epigenetic-regulation-of-the-signature-of-rejection-in-colorectal-cancer
#17
Viktor H Koelzer, Lena Sokol, Stefan Zahnd, Lucine Christe, Heather Dawson, Martin D Berger, Daniel Inderbitzin, Inti Zlobec, Alessandro Lugli
The immune system plays a pivotal role in the development and progression of colorectal cancer (CRC). Tumor immune rejection has been previously linked to the activation of the interferon-stimulated genes (ISG) STAT1, IRF-5 and IRF-1. Specific immunoregulatory microRNAs (miRNAs) may impact the expression of these ISG in the tumor microenvironment. In this translational study, we develop a digital image analysis protocol to identify the ISG-gene expression signature and investigate miRNA expression in the immediate environment of invading cancer cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506896/neurodevelopmental-macpfs-the-vertebrate-astrotactins-and-brinps
#18
REVIEW
Susan R Berkowicz, Aminah Giousoh, Phillip I Bird
Astrotactins (ASTNs) and Bone morphogenetic protein/retinoic acid inducible neural-specific proteins (BRINPs) are two groups of Membrane Attack Complex/Perforin (MACPF) superfamily proteins that show overlapping expression in the developing and mature vertebrate nervous system. ASTN(1-2) and BRINP(1-3) genes are found at conserved loci in humans that have been implicated in neurodevelopmental disorders (NDDs). Here we review the tissue distribution and cellular localization of these proteins, and discuss recent studies that provide insight into their structure and interactions...
May 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28506893/macpf-cdc-proteins-in-development-insights-from-drosophila-torso-like
#19
REVIEW
Travis K Johnson, Michelle A Henstridge, Coral G Warr
The Membrane Attack Complex Perforin-like/Cholesterol-Dependent Cytolysin (MACPF) superfamily is an ancient and biologically diverse group of proteins that are best known for pore-forming roles in mammalian immunity and bacterial pathogenesis. Intriguingly, however, some eukaryotic proteins which contain the MACPF domain that defines this family do not act in attack or defence, and instead have distinct developmental functions. It remains unclear whether these proteins function via pore formation or have a different mechanism of action...
May 12, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28501938/zoledronic-acid-renders-human-m1-and-m2-macrophages-susceptible-to-v%C3%AE-2-%C3%AE-%C3%AE-t-cell-cytotoxicity-in-a-perforin-dependent-manner
#20
Daniel W Fowler, John Copier, Angus G Dalgleish, Mark D Bodman-Smith
Vδ2(+) T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2(+) T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. In this study we focussed on macrophages (Mϕs), as these cells have been shown to take up ZA...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
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