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T cell immunology

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https://www.readbyqxmd.com/read/28811976/long-lived-pancreatic-ductal-adenocarcinoma-slice-cultures-enable-precise-study-of-the-immune-microenvironment
#1
Xiuyun Jiang, Y David Seo, Jae Hyuck Chang, Andrew Coveler, Eslam N Nigjeh, Sheng Pan, Florencia Jalikis, Raymond S Yeung, Ian N Crispe, Venu G Pillarisetty
Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease that is rarely cured, despite many recent successes with immunotherapy for other malignancies. As the human disease is heavily infiltrated by effector T cells, we postulated that accurately modeling the PDA immune microenvironment would allow us to study mechanisms of immunosuppression that could be overcome for therapeutic benefit. Using viable precision-cut slices from fresh PDA, we developed an organotypic culture system for this purpose. We confirmed that cultured slices maintain their baseline morphology, surface area, and microenvironment after at least 6 d in culture, and demonstrated slice survival by MTT assay and by immunohistochemistry staining with Ki-67 and cleaved-Caspase-3 antibodies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811969/k27m-mutant-histone-3-as-a-novel-target-for-glioma-immunotherapy
#2
Katharina Ochs, Martina Ott, Theresa Bunse, Felix Sahm, Lukas Bunse, Katrin Deumelandt, Jana K Sonner, Melanie Keil, Andreas von Deimling, Wolfgang Wick, Michael Platten
Mutation-specific vaccines have become increasingly important in glioma immunotherapy; however, shared neoepitopes are rare. For diffuse gliomas, a driver mutation in the gene for isocitrate dehydrogenase type-1 has been shown to produce an immunogenic epitope currently targeted in clinical trials. For highly aggressive midline gliomas, a recurrent point mutation in the histone-3 gene (H3F3A) causes an amino acid change from lysine to methionine at position 27 (K27M). Here, we demonstrate that a peptide vaccine against K27M-mutant histone-3 is capable of inducing effective, mutation-specific, cytotoxic T-cell- and T-helper-1-cell-mediated immune responses in a major histocompatibility complex (MHC)-humanized mouse model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811898/lentinula-edodes-mycelia-extract-plus-adjuvant-chemotherapy-for-breast-cancer-patients-results-of-a-randomized-study-on-host-quality-of-life-and-immune-function-improvement
#3
Yukiko Nagashima, Shigehumi Yoshino, Shigeru Yamamoto, Noriko Maeda, Tatsuya Azumi, Yoshifumi Komoike, Kiyotaka Okuno, Tsutomu Iwasa, Junji Tsurutani, Kazuhiko Nakagawa, Oka Masaaki, Nagano Hiroaki
Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double-blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, i...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28811631/development-of-a-primary-human-co-culture-model-of-inflamed-airway-mucosa
#4
Lael M Yonker, Hongmei Mou, Kengyeh K Chu, Michael A Pazos, Huimin Leung, Dongyao Cui, Jinhyeob Ryu, Rhianna M Hibbler, Alexander D Eaton, Tim N Ford, J R Falck, T Bernard Kinane, Guillermo J Tearney, Jayaraj Rajagopal, Bryan P Hurley
Neutrophil breach of the mucosal surface is a common pathological consequence of infection. We present an advanced co-culture model to explore neutrophil transepithelial migration utilizing airway mucosal barriers differentiated from primary human airway basal cells and examined by advanced imaging. Human airway basal cells were differentiated and cultured at air-liquid interface (ALI) on the underside of 3 µm pore-sized transwells, compatible with the study of transmigrating neutrophils. Inverted ALIs exhibit beating cilia and mucus production, consistent with conventional ALIs, as visualized by micro-optical coherence tomography (µOCT)...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811625/interleukin-7-in-the-transition-of-bone-marrow-progenitors-to-the-thymus
#5
Adam W Plumb, Abdalla Sheikh, Douglas A Carlow, Hermann J Ziltener, Ninan Abraham
Interleukin-7 (IL-7) is essential for the development of T cells in humans and mice where deficiencies in IL-7 signaling result in severe immunodeficiency. T cells require IL-7 at multiple points during development however it is unclear when IL-7 is first necessary. We observed that mice with impaired IL-7 signaling had a large reduction in the number of early thymic progenitors (ETPs) while mice that overexpress IL-7 had greatly increased numbers of ETPs. These results indicated that the development of ETPs is sensitive to IL-7...
August 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28810825/regulatory-t-cell-levels-in-the-longest-surviving-asian-patient-after-heart-lung-transplant
#6
Lei Huang, Ming Ji, Shounan Yi, Xinmin Zhou
Heart-lung transplant is the most effective therapy for patients with end-stage cardiopulmonary disease. Here, we report an initial assessment of a 31-year-old man who had survived more than 11 years after heart-lung transplant, which represents the longest survival time in this procedure in Asian studies. At his 11th anniversary after transplant, extensive tests were carried out, especially to detect regulatory T-cell levels for the first time in a surviving heart-lung transplant recipient. Preliminarily data revealed the status of his immunologic function in relation to chronic allograft rejection...
August 13, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28808862/a-pilot-study-comparing-t-regulatory-cell-function-among-healthy-children-in-different-areas-of-gansu-china
#7
Panhong Gou, Xiaoru Chang, Zhonghui Ye, Yueli Yao, Patton Khuu Nguyen, Sally Katharine Hammond, Junling Wang, Sa Liu
Immune system is critical to protecting human health from toxic substances. Our previously published research had found an important link between polycyclic aromatic hydrocarbons (PAHs) in ambient air and changes at the DNA level in immune cells that led to impaired function of regulatory T (Treg) cells in children living in California, USA. But molecular and cellular pathways of these changes remain unclear. The present study aims to explore whether exposure to PAHs leads to changes in Treg cells functions of children living in Gansu, China, where ambient air pollution levels are much higher than those in California, and to explore potential mechanisms of PAH-induced immunological dysfunctions...
August 14, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28808358/mbd2-regulates-th17-cell-differentiation-and-experimental-severe-asthma-by-affecting-irf4-expression
#8
Aijun Jia, Yueling Wang, Wenjin Sun, Bing Xiao, Yan Wei, Lulu Qiu, Lin Mu, Li Xu, Jianmin Li, Xiufeng Zhang, Da Liu, Cong Peng, Dongshan Zhang, Xudong Xiang
Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4(+) T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4(+) T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28805806/lung-tumor-exome-files-with-t-cell-receptor-recombinations-a-mouse-model-of-t-cell-infiltrates-reflecting-mutation-burdens
#9
Yaping N Tu, Wei Lue Tong, Timothy J Fawcett, George Blanck
Tumor exomes and RNASeq data were originally intended for obtaining tumor mutations and gene expression profiles, respectively. However, recent work has determined that tumor exome and RNAseq read files contain reads representing T-cell and B-cell receptor (TcR and BcR) recombinations, presumably due to infiltrating lymphocytes. Furthermore, the recovery of immune receptor recombination reads has demonstrated correlations with specific, previously appreciated aspects of tumor immunology. To further understand the usefulness of recovering TcR and BcR recombinations from tumor exome files, we developed a scripted algorithm for recovery of reads representing these recombinations from a previously described mouse model of lung tumorigenesis...
August 14, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28805662/clinical-and-immunological-responses-after-cd30-specific-chimeric-antigen-receptor-redirected-lymphocytes
#10
Carlos A Ramos, Brandon Ballard, Huimin Zhang, Olga Dakhova, Adrian P Gee, Zhuyong Mei, Mrinalini Bilgi, Meng-Fen Wu, Hao Liu, Bambi Grilley, Catherine M Bollard, Bill H Chang, Cliona M Rooney, Malcolm K Brenner, Helen E Heslop, Gianpietro Dotti, Barbara Savoldo
BACKGROUND: Targeting CD30 with monoclonal antibodies in Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) has had profound clinical success. However, adverse events, mainly mediated by the toxin component of the conjugated antibodies, cause treatment discontinuation in many patients. Targeting CD30 with T cells expressing a CD30-specific chimeric antigen receptor (CAR) may reduce the side effects and augment antitumor activity. METHODS: We conducted a phase I dose escalation study in which 9 patients with relapsed/refractory HL or ALCL were infused with autologous T cells that were gene-modified with a retroviral vector to express the CD30-specific CAR (CD30...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28805110/lack-of-interaction-of-lopinavir-solid-drug-nanoparticles-with-cells-of-the-immune-system
#11
Neill J Liptrott, Marco Giardiello, Tom O McDonald, Steven P Rannard, Andrew Owen
AIM: We previously demonstrated that solid drug nanoparticles (SDNs) lopinavir (LPV) dispersed into aqueous media display favorable pharmacokinetics. METHODS: The impact of LPV SDNs on the function and phenotype of primary human T cells and macrophages (primary sites of HIV replication) was investigated. RESULTS: LPV significantly increased IL-1β (ninefold higher than untreated cells; p = 0.045) and TNF-α (sixfold higher than untreated cells; p = 0...
August 14, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28804991/nf-%C3%AE%C2%BAb2-controls-migratory-activity-of-memory-t-cells-by-regulating-expression-of-cxcr4-in-a-mouse-model-of-sj%C3%A3-gren-s-syndrome
#12
Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, Jonathan Sprent, Naozumi Ishimaru
OBJECTIVE: Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T-cell infiltration into target tissues, but the specific chemokines, receptors, and T-cell populations remain largely unidentified. Role of the potent chemokine CXCL12 and its receptor CXCR4 in T-cell autoimmune response was examined using alymphoplasia (aly)/aly mice, a Sjögren's syndrome (SS) model. METHODS: T-cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunological analysis...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28804866/virally-vectored-vaccine-delivery-medical-needs-mechanisms-advantages-and-challenges
#13
Daniel D Pinschewer
Vaccines represent one of the most successful chapters in the history of medicine. Over the past decades, the advent of recombinant cDNA technology has enabled the biomedical community to genetically engineer viruses for vaccine delivery purposes. As a starting point, this review evaluates the unmet medical needs, which drive scientists and industry to exploit such fundamentally new technology for human vaccination. The author discusses the molecular functioning, production and safety profile of replication-competent and -deficient viral vector systems, representing two fundamentally distinct classes of "genetic vaccines"...
August 14, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28804688/pivotal-regulators-of-tissue-homeostasis-and-cancer-macrophages
#14
REVIEW
Yulei Chen, Xiaobo Zhang
Macrophages are an essential component of innate immunity and play a vital role in inflammation and host defense. Based on immunological responses, the macrophages are classified into "activated" macrophage (M1 macrophages) participating in the responses of type I helper T (Th1) cells to pathogens and "alternatively activated" macrophages (M2 macrophages) in response to interleukin (IL)-4 and IL-13. In this review, we discuss the origin, classification and function of macrophages. We also discuss the mechanisms underlying polarization of different macrophage subtypes, including transcriptional, epigenetic and post-transcriptional regulation...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28804488/anti-adhesion-therapies-in-inflammatory-bowel-disease-molecular-and-clinical-aspects
#15
REVIEW
Sebastian Zundler, Emily Becker, Carl Weidinger, Britta Siegmund
The number of biologicals for the therapy of immunologically mediated diseases is constantly growing. In contrast to other agents that were previously introduced in rheumatologic or dermatologic diseases and only later adopted for the treatment of inflammatory bowel diseases (IBDs), the field of IBD was ground breaking for the concept of anti-adhesion blockade. Anti-adhesion antibodies selectively target integrins controlling cell homing to the intestine, which leads to reduction of inflammatory infiltration to the gut in chronic intestinal inflammation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28802664/cytokines-and-soluble-hla-g-levels-in-bone-marrow-stroma-and-their-association-with-the-survival-rate-of-patients-exhibiting-childhood-t-cell-acute-lymphoblastic-leukemia
#16
Renata Dos Santos Almeida, Alessandra Maria de Luna Ramos, Carlos Feitosa Luna, Francisco Pedrosa, Eduardo Antônio Donadi, Norma Lucena-Silva
Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase...
August 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28802495/the-immunology-of-melanoma
#17
REVIEW
Jennifer S Ko
The relatively high DNA mutational burden in melanoma allows for the creation of potentially "foreign," immune-stimulating neoantigens, and leads to its exceptional immunogenicity. Brisk tumor-infiltrating lymphocytes, a marker of immune editing, confer improved overall survival in melanoma, possibly due to reduced sentinel lymph node spread. Meanwhile, T-cell-stimulating drugs, so-called T-cell checkpoint inhibitors, which reverse peripheral tolerance-dependent tumor escape, have demonstrated unparalleled clinical success in metastatic melanoma...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28802077/helicobacter-pylori-and-its-secreted-immunomodulator-vaca-protect-against-anaphylaxis-in-experimental-models-of-food-allergy
#18
Andreas Kyburz, Sabine Urban, Aleksandra Altobelli, Stefan Floess, Jochen Huehn, Timothy L Cover, Anne Müller
BACKGROUND: Food allergy is an increasingly common health problem in Western populations. Epidemiological studies have suggested both positive and negative associations between food allergy and infection with the gastric bacterium Helicobacter pylori. OBJECTIVE: The objective of this work was to investigate whether experimental infection with H. pylori, or prophylactic treatment with H. pylori-derived immunomodulatory molecules, affects the onset and severity of food allergy, either positively or negatively...
August 12, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28801931/immunomodulatory-effects-of-adipose-stromal-vascular-fraction-cells-promote-alternative-activation-macrophages-to-repair-tissue-damage
#19
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Isabella Febbo, Bruce A Bunnell
The pathogenesis of many diseases is driven by the interactions between helper T (TH ) cells and macrophages. The phenotypes of these cells are a functional dichotomy that are persuaded according to the surrounding milieu. In both multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model, TH 1 and TH 17 cells propagate autoimmune signaling and inflammation in the peripheral lymphoid tissues. In turn, this pro-inflammatory repertoire promotes the classical activation, formerly the M1-type, macrophages...
August 12, 2017: Stem Cells
https://www.readbyqxmd.com/read/28799908/the-molecular-basis-of-erythrocyte-invasion-by-malaria-parasites
#20
REVIEW
Alan F Cowman, Christopher J Tonkin, Wai-Hong Tham, Manoj T Duraisingh
Plasmodium species cause malaria by proliferating in human erythrocytes. Invasion of immunologically privileged erythrocytes provides a relatively protective niche as well as access to a rich source of nutrients. Plasmodium spp. target erythrocytes of different ages, but share a common mechanism of invasion. Specific engagement of erythrocyte receptors defines target cell tropism, activating downstream events and resulting in the physical penetration of the erythrocyte, powered by the parasite's actinomyosin-based motor...
August 9, 2017: Cell Host & Microbe
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