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https://www.readbyqxmd.com/read/28099196/use-of-engineered-exosomes-expressing-hla-and-costimulatory-molecules-to-generate-antigen-specific-cd8-t-cells-for-adoptive-cell-therapy
#1
Sueon Kim, Hyun-Jung Sohn, Hyun-Joo Lee, Dae-Hee Sohn, Seung-Joo Hyun, Hyun-Il Cho, Tai-Gyu Kim
Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells...
January 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28099147/ctla-4-positive-breast-cancer-cells-suppress-dendritic-cells-maturation-and-function
#2
Xi Chen, Qianqian Shao, Shengnan Hao, Zhonghua Zhao, Yang Wang, Xiaofan Guo, Ying He, Wenjuan Gao, Haiting Mao
Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a potent immunoregulatory molecule, can down-regulate T-cell activation and inhibit anti-tumor immune response. This study showed that LPS-stimulated human dendritic cells (DCs) decreased the expression of HLA-DR, CD83 and costimulatory molecules (CD40, CD80 and CD86) following coculturing with CTLA-4+ breast cancer cells. Moreover, the suppressed DCs further inhibited proliferation of allogeneic CD4+/CD8+ T-cells, differentiation of Th1 and function of cytotoxic lymphocytes (CTLs)...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#3
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096174/anti-folate-receptor-%C3%AE-ige-but-not-igg-recruits-macrophages-to-attack-tumors-via-tnf-%C3%AE-mcp-1-signaling
#4
Debra H Josephs, Heather J Bax, Tihomir Dodev, Mirella Georgouli, Mano Nakamura, Giulia Pellizzari, Louise Saul, Panagiotis Karagiannis, Anthony Cheung, Cecilia Herraiz, Kristina M Ilieva, Isabel Correa, Matthew Fittall, Silvia Crescioli, Patrycja Gazinska, Natalie Woodman, Silvia Mele, Giulia Chiaruttini, Amy E Gilbert, Alexander Koers, Marguerite Bracher, Christopher Selkirk, Heike Lentfer, Claire Barton, Elliott Lever, Gareth Muirhead, Sophia Tsoka, Silvana Canevari, Mariangela Figini, Ana Montes, Noel Downes, David Dombrowicz, Christopher Corrigan, Andrew J Beavil, Frank O Nestle, Paul S Jones, Hannah J Gould, Victoria Sanz-Moreno, Philip J Blower, James Spicer, Sophia N Karagiannis
IgE antibodies are key mediators of anti-parasitic immune responses, but their potential for cancer treatment via antibody-directed cell-mediated cytotoxicity (ADCC) has been little studied. Recently, tumor antigen-specific IgEs were reported to restrict cancer cell growth by engaging high-affinity Fc receptors on monocytes and macrophages, however, the underlying therapeutic mechanisms were undefined and in vivo proof-of-concept was limited. Here, an immunocompetent rat model was designed to recapitulate the human IgE-Fcε receptor system for cancer studies...
January 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28094582/effects-of-arsenic-on-porcine-dendritic-cells-in-vitro
#5
Jalil Mehrzad, Mohamad Hosein Mahmudy Gharaie, Masumeh Taheri
Exposure to arsenic (As) is an ongoing, and in some places increasing, health problem. Still, however, the effects of As exposure on the immune system are not well understood. Dendritic cells (DC) are a critical immune cell that bridges the innate and adaptive immune systems. To determine the impact of inorganic (i)As exposure on DC, the effects of (geo)anthropogenically relevant levels of NaAsO2 on the function of porcine monocyte-derived DC (MoDC) were evaluated in an in vitro model. The results showed a low dose of iAs reduced the phagocytic capacity of MoDC...
January 17, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28076241/phenotypic-and-functional-characteristics-of-hla-dr-neutrophils-in-brazilians-with-cutaneous-leishmaniasis
#6
Richard E Davis, Smriti Sharma, Jacilara Conceição, Pedro Carneiro, Fernanda Novais, Phillip Scott, Shyam Sundar, Olivia Bacellar, Edgar M Carvalho, Mary E Wilson
The protozoan Leishmania braziliensis causes cutaneous leishmaniasis (CL) in endemic regions. In murine models, neutrophils (PMNs) are recruited to the site of infection soon after parasite inoculation. However, the roles of neutrophils during chronic infection and in human disease remain undefined. We hypothesized that neutrophils help maintain a systemic inflammatory state in subjects with CL. Lesion biopsies from all patients with CL tested contained neutrophils expressing HLA-DR, a molecule thought to be restricted to professional antigen-presenting cells...
October 17, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28075416/phosphorylated-radix-cyathulae-officinalis-polysaccharides-act-as-adjuvant-via-promoting-dendritic-cell-maturation
#7
Haibo Feng, Sean P McDonough, Jing Fan, Shiping Yang, Xuelian Zhao, Yong Lu, Yun Gan, Xiao Yi, Yung-Fu Chang
The aim of this study was to investigate whether phosphorylated Radix Cyathulae officinalis Kuan polysaccharides (pRCPS) used as adjuvant with foot-and-mouth disease vaccine (FMDV) can stimulate specific humoral and cellular immune responses in ICR mice. The results demonstrated that pRCPS significantly up-regulated FMDV-specific IgG, IgG1, IgG2b and IgG2a antibody levels and splenocyte proliferation. pRCPS also promoted the killing activities of cytotoxic T lymphocytes (CTL) and natural killer cells (NK). In addition, pRCPS enhanced the expression levels of IL-2, IL-4, and IFN-γ in CD4⁺ T cells and the level of IFN-γ in CD8⁺ T cells...
January 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28070458/characterization-of-adipose-tissue-macrophages-and-adipose-derived-stem-cells-in-critical-wounds
#8
Bong-Sung Kim, Pathricia V Tilstam, Katrin Springenberg-Jung, Arne Hendrick Boecker, Corinna Schmitz, Daniel Heinrichs, Soo Seok Hwang, Jan Philipp Stromps, Bergita Ganse, Ruedger Kopp, Matthias Knobe, Juergen Bernhagen, Norbert Pallua, Richard Bucala
BACKGROUND: Subcutaneous adipose tissue is a rich source of adipose tissue macrophages and adipose-derived stem cells which both play a key role in wound repair. While macrophages can be divided into the classically-activated M1 and the alternatively-activated M2 phenotype, ASCs are characterized by the expression of specific stem cell markers. METHODS: In the present study, we have investigated the expression of common macrophage polarization and stem cell markers in acutely inflamed adipose tissue...
2017: PeerJ
https://www.readbyqxmd.com/read/28067853/capparis-spinosa-fruit-ethanol-extracts-exert-different-effects-on-the-maturation-of-dendritic-cells
#9
Azeguli Hamuti, Jinyu Li, Fangfang Zhou, Adila Aipire, Ji Ma, Jianhua Yang, Jinyao Li
Capparis spinosa L. (C. spinosa) has been used as food and traditional medicine and shows anti-inflammatory and anti-oxidant activities. Here, we prepared the C. spinosa fruit ethanol extracts (CSEs) using different procedures and investigated the effects of CSE on the maturation of mouse bone marrow-derived dendritic cells (DCs) in the absence or presence of lipopolysaccharide (LPS). DC maturation and cytokine production were detected by flow cytometry and ELISA, respectively. We obtained three different CSEs and dissolved in water or DMSO, named CSE2W, CSEMW, CSE3W, CSE2D, CSEMD, and CSE3D, respectively...
January 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28067413/echinacea-purpurea-extract-polarizes-m1-macrophages-in-murine-bone-marrow-derived-macrophages-through-the-activation-of-jnk
#10
Aikun Fu, Yang Wang, Yanping Wu, Hongliang Chen, Shasha Zheng, Yali Li, Xin Xu, Weifen Li
Echinacea purpurea is an indigenous North American purple cone flower used by North Americans for treatment of various infectious diseases and wounds. This study investigated the effect of polysaccharide enriched extract of Echinacea purpurea (EE) on the polarization of macrophages. The results showed that 100 µg/mL of EE could markedly activate the macrophage by increasing the expression of CD80, CD86, and MHCII molecules. Meanwhile, EE upregulated the markers of classically activated macrophages (M1) such as CCR7 and the production of IL-1β, IL-6, IL-12p70, TNF-αand NO...
January 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28057573/characterization-of-polysaccharides-extracted-from-platycodon-grandiflorus-jacq-a-dc-affecting-activation-of-chicken-peritoneal-macrophages
#11
Pimiao Zheng, Wentao Fan, Shenghua Wang, Pan Hao, Yang Wang, Huiyu Wan, Zhihui Hao, Jianzhu Liu, Xiaona Zhao
Polysaccharides were isolated from Platycodon grandiflorus (Jacq.) A.DC. (PG) and the effects of three polysaccharides (PGPS80, PGPS60, PGPSt) on their immunological activities were studied. The structure identification of PGPSs was assessed using physicochemical and spectral methods. Results showed that PGPSt(2.67×10(5)Da) compared to PGPS80(1.01×10(5)Da) and PGPS60(1.12×10(5)Da) has relatively higher average molecular weight(Mw) at the first peak with a narrower molecular weight distribution and all consisted of glucose, mannose, arabinose, galactose, xylose and rhamnose in different mass percentages...
January 2, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28053234/tcr-signaling-and-cd28-ctla-4-signaling-cooperatively-modulate-t-regulatory-cell-homeostasis
#12
Michael P Holt, George A Punkosdy, Deborah D Glass, Ethan M Shevach
Foxp3(+) T regulatory cells (Tregs), conventional CD4(+)Foxp3(-) T cells, and CD8(+) T cells represent heterogeneous populations composed of naive phenotype (NP, CD44(low)) and memory phenotype (MP, CD44(high)) subpopulations. NP and MP subsets differ in their activation state, contribution to immune function, and capacity to proliferate in vivo. To further understand the factors that contribute to the differential homeostasis of NP/MP subsets, we examined the differential effects of CD28 and CTLA-4 interaction with CD80/CD86, as well as MHC class II-TCR interaction within mouse Treg pools and CD4(+) and CD8(+) T cell pools...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28052009/cancer-associated-fibroblasts-promote-an-immunosuppressive-microenvironment-through-the-induction-and-accumulation-of-protumoral-macrophages
#13
Hideyuki Takahashi, Koichi Sakakura, Takeshi Kudo, Minoru Toyoda, Kyoichi Kaira, Tetsunari Oyama, Kazuaki Chikamatsu
Stromal cells in the tumor microenvironment (TME) closely interact with tumor cells and affect tumor cell behavior in diverse manners. We herein investigated the mechanisms by which cancer-associated fibroblasts (CAFs) affect the functional polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC) in vitro and in human cancer samples. The expression of CD68, CD14, CD163, CD200R, CD206, HLA-G, CD80, and CD86 was higher in CD14-positive cells co-cultured with the culture supernatants of CAFs established from OSCC specimens (CAF-educated cells) than in control cells...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/28040582/folate-deficiency-affects-dendritic-cell-function-and-subsequent-t-helper-cell-differentiation
#14
Chi-Heng Wu, Tzu-Chien Huang, Bi-Fong Lin
Insufficient folate status may be related to the increasing prevalence of immune- or inflammation-related chronic diseases. To investigate the effects of folate on immune regulation, we examined the impact of folate deficiency (FD) on dendritic cell (DC) maturation and function and, thus, T helper (Th) cells differentiation. First, bone marrow-derived DCs (BMDCs) were generated from BALB/c mice bone marrow cells cultured in folate-containing (F-BMDCs) or folate-deficient (FD-BMDCs) medium. FD-BMDC displayed more immature phenotype including reduced levels of major histocompatibility complex class II (MHC II), co-stimulatory molecules and characteristic of higher endocytic activity...
November 20, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28038796/cyclophilin-a-mediates-the-ox-ldl-induced-activation-and-apoptosis-of-macrophages-via-autophagy
#15
Zhiqiang Xue, Wei Yuan, Jing Li, Hong Zhou, Lihua Xu, Jiayi Weng, Xiaoyang Li, Xinru Zhang, Zhongqun Wang, Jinchuan Yan
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) is the most common inflammatory factor that mediates the activation and apoptosis of macrophages. Cyclophilin A (CyPA) is expressed following oxidative stress, hypoxia, and infection. However, the role of CyPA in the activation and apoptosis of macrophages is unclear. The aims of the study were to determine whether CyPA mediates the ox-LDL-induced activation and apoptosis in RAW264.7 cells and to analyze potential mechanisms. METHODS AND RESULTS: Through Western blot and ELISA test, the expression of CyPA induced by ox-LDL is time-dependent in RAW264...
December 19, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28028922/n-dihydrogalactochitosan-as-a-potent-immune-activator-for-dendritic-cells
#16
Ahmed El-Hussein, Samuel S K Lam, Joseph Raker, Wei R Chen, Michael R Hamblin
Immunotherapy has become one of the fastest growing areas of cancer research. A promising in situ autologous cancer vaccine (inCVAX) uses a novel immune activator, N-dihydrogalactochitosan (GC), that possesses the ability to stimulate dendritic cells (DC). inCVAX is a combination treatment procedure involving treatment of the tumor with a thermal near-infrared laser to liberate whole cell tumor antigens, followed by injection of GC (a glucosamine polymer with galactose attached to the amino groups) into the treated tumor thereby inducing a systemic anti-tumor immune response...
December 28, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28017828/effect-of-dezocine-on-il-12-and-il-10-secretion-and-lymphocyte-activation-by-culturing-dendritic-cells-from-human-umbilical-cord-blood
#17
Chang Feng, Man Feng, Ran Jiao, Dongyi Liu, Yanwu Jin, Xin Zhao, Ruixue Xiao
Dezocine has been generally utilized for pain therapy and auxiliary anesthesia. Although it has some advantages on the prevention of some anesthesia related complications, its effect on immune responses remains unclear. Our study investigated the effects of Dezocine on IL-10 and IL-12 secretion and lymphocytes activation by culturing dendritic cells (DCs), and revealed the underlying mechanism. Mononuclear cells were divided into negative control group (GN), positive control group (GP), experimental group (GD; GD5, D7, D9)...
December 22, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28017428/the-induction-of-cd80-and-apoptosis-on-b-cells-and-cd40l-in-cd4-t-cells-in-response-to-seasonal-influenza-vaccination-distinguishes-responders-versus-non-responders-in-healthy-controls-and-aviremic-art-treated-hiv-infected-individuals
#18
Anna M Powell, Zhenwu Luo, Lisa Martin, Zhuang Wan, Lei Ma, Guoyang Liao, Yuxia Song, Xiaochun Li, J Michael Kilby, Lei Huang, Wei Jiang
BACKGROUND: Studies have shown that HIV infection is associated with an impaired influenza vaccine response. We examined the role of cellular phenotypes and function in influenza vaccine responsiveness in healthy controls and aviremic HIV-infected subjects on antiretroviral treatment (ART). METHODS: 16 healthy controls and 26 ART+ aviremic HIV+ subjects were enrolled in the current study. Blood was collected at pre-vaccination (D0), and on days 7-10 (D7) and 14-21 (D14) following the 2013-2014 seasonal influenza vaccine administrations...
December 22, 2016: Vaccine
https://www.readbyqxmd.com/read/28005579/spontaneous-activation-of-antigen-presenting-cells-by-genes-encoding-truncated-homo-oligomerizing-derivatives-of-cd40
#19
Noam Levin, Aviad Pato, Gal Cafri, Galit Eisenberg, Tamar Peretz, Alon Margalit, Michal Lotem, Gideon Gross
The interaction between the CD40 receptor on antigen-presenting cells (APCs) and its trimeric ligand on CD4 T cells is essential for the initiation and progression of the adaptive immune response. Here we undertook to endow CD40 with the capacity to trigger spontaneous APC activation through ligand-independent oligomerization. To this end we exploited the GCN4 yeast transcriptional activator, which contains a leucine zipper DNA-binding motif that induces homophilic interactions. We incorporated GCN4 variants forming homodimers, trimers, or tetramers at the intracellular domain of human and mouse CD40 and replaced the extracellular portion with peptide-β2m or other peptide tags...
December 21, 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27999734/molecular-and-clinical-characterization-of-pd-l1-expression-at-transcriptional-level-via-976-samples-of-brain-glioma
#20
Zheng Wang, Chuanbao Zhang, Xing Liu, Zhiliang Wang, Lihua Sun, Guanzhang Li, Jingshan Liang, Huimin Hu, Yanwei Liu, Wei Zhang, Tao Jiang
Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice. Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available...
2016: Oncoimmunology
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