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Zhang Yiwen, Gao Shilin, Chen Yingshi, Su Lishi, Luo Baohong, Liu Chao, Li Linghua, Pan Ting, Zhang Hui
Efficient antigen presentation is indispensable for cytotoxic T lymphocyte (CTL)-mediated immunotherapy. B-lymphocytes propagated with CD40L have been developed as antigen-presenting cells (APCs), but this capacity needs further optimization. Here, we aimed to expand human B-lymphocytes on a large scale while maintaining their antigen-presenting ability by using both CD40L and B-cell activating factor (BAFF). The addition of BAFF enhanced the expansion efficiency and prolonged the culture time without causing apoptosis of the expanded B-cells...
October 21, 2016: Oncotarget
Davinia Pla, Libia Sanz, Mahmood Sasa, Manuel E Acevedo, Quetzal Dwyer, Jordi Durban, Alicia Pérez, Yania Rodriguez, Bruno Lomonte, Juan J Calvete
: Bothriechis is a genus of eleven currently recognized slender and arboreal venomous snakes, commonly called palm-pitvipers that range from southern Mexico to northern South America. Despite dietary studies suggesting that palm-pitvipers are generalists with an ontogenetic shift toward endothermic prey, venom proteomic analyses have revealed remarkable divergence between the venoms of the Costa Rican species, B. lateralis, B. schlegelii, B. supraciliaris, and B. nigroviridis. To achieve a more complete picture of the venomic landscape across Bothriechis, the venom proteomes of biodiversity of the northern Middle American highland palm-pitvipers, B...
October 21, 2016: Journal of Proteomics
Cameron Browne
This paper concerns modeling the coupled within-host population dynamics of virus and CTL (Cytotoxic T Lymphocyte) immune response. There is substantial evidence that the CTL immune response plays a crucial role in controlling HIV in infected patients. Recent experimental studies have demonstrated that certain CTL variants can recognize HIV infected cells early in the infected cell lifecycle before viral production, while other CTLs only detect viral proteins (epitopes) presented on the surface of infected cells after viral production...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
Lei Wang, Na Peng, Xiaoyan Hu, Wentao Liang, Kai Liang, Guizhu Peng
Objective To evaluate the effects of cryopreservation on the proliferation and killing activity of lymphocytes, and explore a novel protocol of preparing autologous mouse cytotoxic T lymphocytes (CTLs). Methods Mononuclear cells derived from spleen (5.0×10(6)/mL) were cryopreserved in CELLBANKER2 for 6 days and recovered in water bath at 39DegreesCelsius. The fresh lymphocytes and post-cryopreservation lymphocytes were induced by CD3 mAb (100 ng/mL) and recombinant mouse interleukin 2 (rmIL-2, 100 ng/mL) to obtain cytokine-induced killer cells (CIKs)...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Eiji Matsuura, Yoshimi Enose-Akahata, Karen Yao, Unsong Oh, Yuetsu Tanaka, Hiroshi Takashima, Steven Jacobson
Pathology of HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP) is believed to be the result of "bystander damage" involving effector CD8 (+) T lymphocytes (CTLs) killing of virus infected cells. But the specific cellular events leading up to tissue injury are still unclear. Here, we developed the Microscopy Imaging of Cytotoxic T lymphocyte assay with Fluorescence emission (MI-CaFé), an optimized visualization analysis to explore the interactions between CTLs and virus infected or viral antigen presenting target cells...
October 3, 2016: Journal of Neuroimmunology
Zhihao Jia, Huan Zhang, Shuai Jiang, Mengqiang Wang, Lingling Wang, Linsheng Song
C-type lectins (CTLs), a superfamily of Ca(2+)-dependent carbohydrate-recognition proteins, are involved in nonself-recognition and pathogen elimination, and play crucial roles in the innate immunity. In the present study, two single CRD C-type lectins, CgCLec-4 and CgCLec-5, were identified from oyster Crassostrea gigas. The open reading frame (ORF) of CgCLec-4 and CgCLec-5 encoded polypeptides of 152 and 150 amino acids, respectively. Both CgCLec-4 and CgCLec-5 contained one CRD with six conserved cysteines to form three disulfide bridges...
October 17, 2016: Fish & Shellfish Immunology
Wataru Obara, Takashi Karashima, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Keiji Inoue, Toyomasa Katagiri, Taro Shuin, Yusuke Nakamura, Tomoaki Fujioka
PURPOSE: Through genome-wide expression profile analysis, hypoxia-inducible protein 2 (HIG2) has previously been identified as an oncoprotein involved in development/progression of renal cell carcinoma (RCC). We subsequently identified a highly immunogenic HLA-A*0201/0206-restricted epitope peptide (HIG2-9-4) corresponding to a part of HIG2 and applied it as a therapeutic vaccine. We conducted a phase I clinical trial using the HIG2-9-4 peptide for patients with advanced RCC. MATERIALS AND METHODS: Nine patients having HLA-A*0201 or HLA-A*0206 with metastatic or unresectable RCC after failure of the cytokine and/or tyrosine kinase inhibitor therapies were enrolled in this study...
October 18, 2016: Cancer Immunology, Immunotherapy: CII
Mahzad Akbarpour, Abdelnaby Khalyfa, Zhuanghong Qiao, Alex Gileles-Hillel, Isaac Almendros, Ramon Farré, David Gozal
STUDY OBJECTIVE: The presence of obstructive sleep apnea (OSA) in patients with cancer appears to be accompanied by poorer outcomes. However, the mechanisms underlying such association are unknown. Tumor infiltrating lymphocytes (TILs), including CD8+ T cells, function as cytotoxic T lymphocytes (CTLs), and mount immune responses to cancer by the release of cytolytic enzymes, including granzyme B (GzmB), perforin (Prf) and cytokines such as interferon (IFN)-γ. METHODS: Using established in vivo mouse models, we investigated CD8+ T cells and cancer stem cells (CSC) in intermittent hypoxia (IH) and sleep fragmentation (SF) in the context of tumor environment...
October 10, 2016: Sleep
Noriyoshi Iriyama, Yoshihiro Hatta, Masami Takei
It has been shown that an increase in cytotoxic lymphocyte counts in the peripheral blood occurs rapidly after taking dasatinib, but the underlying mechanism is not yet elucidated. To investigate the influence of dasatinib on signal transduction pathways, we investigated the changes in JAK-STAT, mitogen-activated protein kinase (MAPK), and AKT in cytotoxic lymphocytes, including natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), before and after dasatinib treatment in chronic myeloid leukemia patients...
October 10, 2016: Cancer Medicine
Yi Yang, Jing Lu, Hangfan Liu, Guoguo Jin, Ruihua Bai, Xiang Li, Dongyu Wang, Jimin Zhao, Youtian Huang, Kangdong Liu, Ying Xing, Ziming Dong
Dendritic cells (DC) have been exploited for vaccination against cancer for years. DC loading autologous tumor lysate (ATL-DC) have been assessed in ongoing clinical trials, but frequently do not meet expectation. In this study, we found that mice immunized with ATL-DC induced less protective anti-tumor effect than immunized with DC alone. The percentage of CD8(+) T cells and the lysis efficiency of CTLs to auto tumor cells in ATL-DC vaccination group was less than that of DC group. Moreover, vaccination of mice with ATL-DC also promoted tumor angiogenesis by analyzing the CD31 positive microvessel density and hemoglobin content of tumor specimens...
October 10, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jian-Fei Tu, Ya-Hui Ding, Xi-Hui Ying, Fa-Zong Wu, Xin-Mu Zhou, Deng-Ke Zhang, Hai Zou, Jian-Song Ji
Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3(+), CD4(+), and CD8(+) cytotoxic lymphocytes (CTLs) as well as CD56(+) NK cells and CD68(+) macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3(+) (FOXP3(+)) Tregs were found in intratumoural tissue...
October 11, 2016: Scientific Reports
Anning Li, Yue Wu, Jenny Linnoila, Benjamin Pulli, Cuihua Wang, Matthias Zeller, Muhammad Ali, Grant K Lewandrowski, Jinghui Li, Benoit Tricot, Edmund Keliher, Gregory R Wojtkiewicz, Giulia Fulci, Xiaoyuan Feng, Bakhos A Tannous, Zhenwei Yao, John W Chen
Currently, there is no stable and flexible method to label and track cytotoxic T lymphocytes (CTLs) in vivo in CTL immunotherapy. We aimed to evaluate whether the sulfo-hydroxysuccinimide (NHS)-biotin-streptavidin (SA) platform could chemically modify the cell surface of CTLs for in vivo tracking. CD8+ T lymphocytes were labeled with sulfo-NHS-biotin under different conditions and then incubated with SA-Alexa647. Labeling efficiency was proportional to sulfo-NHS-biotin concentration. CD8+ T lymphocytes could be labeled with higher efficiency with sulfo-NHS-biotin in DPBS than in RPMI (P < 0...
October 8, 2016: Cancer Immunology, Immunotherapy: CII
Guido Wabnitz, Emre Balta, Yvonne Samstag
T-cells need to be tightly regulated during their activation and effector phase to assure an appropriate defence against cancer or pathogens and - vice versa - to avoid autoimmune reactions. Regulatory signals are provided via the immune synapse between T-cells and antigen-presenting cells (APCs) or target cells. The stability and kinetics of immune synapse formation is critical for proper T-cell functions. It requires dynamic rearrangements of the actin cytoskeleton necessary for organized spatio-temporal redistribution of receptors and adhesion molecules...
September 27, 2016: Advances in Biological Regulation
Kayoko Waki, Akira Yamada
High Mobility Group Box 1 (HMGB1) is a member of the damage-associated molecular patterns (DAMPs), which cause inflammation and trigger innate immunity through Toll-like receptors (TLRs) 2/4 and the receptor for advanced glycation end products (RAGE). We examined the effect of glycyrrhizin, a selective inhibitor of HMGB1, on the induction of cytotoxic T-lymphocytes (CTLs) in mice. B6 mice, either OT-1 spleen cell-transferred or untransferred, were immunized with an s.c. injection of OVA257-264 peptide with topical imiquimod, and glycyrrhizin was mixed with the antigen peptide...
September 22, 2016: Cancer Science
X Z Li, Y Han, J Tian, X Ren, X Ma, M Ma
To determine the cytotoxic effect of lymphocytes activated by melanoma-associated antigen 3 (MAGE-3)-sensitized dendritic cells (DCs) on BIU-87 tumor cells, and to evaluate the possibility of MAGE-3-peptide-pulsed DCs as a vaccine in bladder cancer immunotherapy, the proliferation of T cells and the activity of cytotoxic T lymphocytes (CTLs) were examined by the MTT method. CTLs were induced by MAGE-3-sensitized DCs, or by ovalbumin (OVA) peptide and non-sensitized DCs as controls, respectively. The results indicated that MAGE-3-sensitized DCs have the ability to promote the proliferation of T cells as well as the cytotoxic activity of CTLs on bladder cancer cells in comparison with OVA peptide and non-sensitized DCs...
August 30, 2016: Genetics and Molecular Research: GMR
Katrina A Lythgoe, François Blanquart, Lorenzo Pellis, Christophe Fraser
The viral population of HIV-1, like many pathogens that cause systemic infection, is structured and differentiated within the body. The dynamics of cellular immune trafficking through the blood and within compartments of the body has also received wide attention. Despite these advances, mathematical models, which are widely used to interpret and predict viral and immune dynamics in infection, typically treat the infected host as a well-mixed homogeneous environment. Here, we present mathematical, analytical, and computational results that demonstrate that consideration of the spatial structure of the viral population within the host radically alters predictions of previous models...
October 2016: PLoS Biology
Joanna B Pawlak, Brett J Hos, Michel J van de Graaff, Otty A Megantari, Nico Meeuwenoord, Herman S Overkleeft, Dmitri V Filippov, Ferry Ossendorp, Sander I van Kasteren
Antigen recognition followed by the activation of cytotoxic T-cells (CTLs) is a key step in adaptive immunity, resulting in clearance of viruses and cancers. The repertoire of peptides that have the ability to bind to the major histocompatibility type-I (MHC-I) is enormous, but the available approaches to study the diversity of the peptide repertoire on a cell are limited. Here we explore the use of bioorthogonal chemistry to quantify specific peptide-MHC-I complexes (pMHC-I) on cells. We show that modifying epitope peptides with bioorthogonal groups in surface accessible positions allows wild-type-like MHC-I binding and bioorthogonal ligation using fluorogenic chromophores in combination with a Cu(I)-catalyzed Huisgen cycloaddition reaction...
October 5, 2016: ACS Chemical Biology
Soheila Moeini, Mohsen Saeidi, Fatemeh Fotouhi, Mahdieh Mondanizdeh, Sadegh Shirian, Alireza Mohebi, Ali Gorji, Amir Ghaemi
The use of DNA vaccines has become an attractive approach for generating antigen-specific cytotoxic CD8(+) T lymphocytes (CTLs), which can mediate protective antitumor immunity. The potency of DNA vaccines encoding weakly immunogenic tumor-associated antigens (TAAs) can be improved by using an adjuvant injected together with checkpoint antibodies. In the current study, we evaluated whether the therapeutic effects of a DNA vaccine encoding human papilloma virus type 16 (HPV-16) E7 can be enhanced by combined application of an immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway and secondary lymphoid tissue chemokine (SLC) also known as CCL21 adjuvant, in a mouse cervical cancer model...
October 3, 2016: Archives of Virology
Julian Mackay-Wiggan, Ali Jabbari, Nhan Nguyen, Jane E Cerise, Charlotte Clark, Grace Ulerio, Megan Furniss, Roger Vaughan, Angela M Christiano, Raphael Clynes
BACKGROUND. Alopecia areata (AA) is a common autoimmune disease with a lifetime risk of 1.7%; there are no FDA-approved treatments for AA. We previously identified a dominant IFN-γ transcriptional signature in cytotoxic T lymphocytes (CTLs) in human and mouse AA skin and showed that treatment with JAK inhibitors induced durable hair regrowth in mice by targeting this pathway. Here, we investigated the use of the oral JAK1/2 inhibitor ruxolitinib in the treatment of patients with moderate-to-severe AA. METHODS...
September 22, 2016: JCI Insight
Yuta Yoshizaki, Eiji Yuba, Toshihiro Komatsu, Keiko Udaka, Atsushi Harada, Kenji Kono
To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAPβA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs)...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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