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https://www.readbyqxmd.com/read/27915371/histone-deacetylase-inhibitors-deplete-myeloid-derived-suppressor-cells-induced-by-4t1-mammary-tumors-in-vivo-and-in-vitro
#1
Hai-Fang Wang, Fen Ning, Zong-Cai Liu, Long Wu, Zi-Qian Li, Yi-Fei Qi, Ge Zhang, Hong-Sheng Wang, Shao-Hui Cai, Jun Du
Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells that suppress anti-tumor immunity. MDSC are increased in tumor-bearing hosts; thus, depletion of MDSC may enhance anti-tumor immunity. Histone deacetylase inhibitors (HDACi) are chemical agents that are primarily used against hematologic malignancies. The ability of these agents to modulate anticancer immunity has recently been extensively studied. However, the effect of HDACi on MDSC has remained largely unexplored...
December 3, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27914086/killing-bacteria-with-cytotoxic-effector-proteins-of-human-killer-immune-cells-granzymes-granulysin-and-perforin
#2
Diego López León, Isabelle Fellay, Pierre-Yves Mantel, Michael Walch
Bacterial pathogens represent a constant threat to human health that was exacerbated in recent years by a dramatic increase of strains resistant to last resort antibiotics. The immune system of higher vertebrates generally evolved several efficient innate and adaptive mechanisms to fight ubiquitous bacterial pathogens. Among those mechanisms, immune proteases were recognized to contribute essentially to antibacterial immune defense. The effector serine proteases of the adaptive immune system, the granzymes, exert potent antimicrobial activity when they are delivered into the bacterial cytosol by prokaryotic membrane disrupting proteins, such as granulysin...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27912146/inosine-acedoben-dimepranol-promotes-an-early-and-sustained-increase-in-the-natural-killer-cell-component-of-circulating-lymphocytes-a-clinical-trial-supporting-anti-viral-indications
#3
S Rumel Ahmed, Amy S Newman, James O'Daly, Sean Duffy, Gillian Grafton, Catherine A Brady, S John Curnow, Nicholas M Barnes, John Gordon
Inosine Acedoben Dimepranol (IAD), licensed for the treatment of cell-mediated immune deficiencies associated with viral infections, has been reported to impact a variety of immune parameters both in vitro and in vivo. Here we report the results from a clinical trial where multiple lymphocyte subsets - CD19+ B cells, CD3+ T cells, CD4+ T-helper cells, FoxP3(hi)/CD25(hi)/CD127(lo) regulatory T cells (Tregs), CD3-/CD56+ NK cells, and CD3+/CD56+ NKT cells - were, together with serum immunoglobulins and IgG subclasses, followed during 14days of IAD administration to ten healthy volunteers; these selected from 27 individuals pre-screened in vitro for their capacity to respond to IAD as gauged by increases in the percentage of Treg and/or NKT cells arising in PHA-stimulated cultures...
November 29, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27906831/bos-is-associated-with-increased-cytotoxic-pro-inflammatory-cd8-t-nkt-like-and-nk-cells-in-the-small-airways
#4
Greg Hodge, Sandra Hodge, Aeneas Yeo, Phan Nguyen, Emily Hopkins, Holmes-Liew Cl, Paul N Reynolds, Mark Holmes
BACKGROUND: Immunosuppression therapy following lung transplantation fails to prevent bronchiolitis obliterans syndrome (BOS) in many patients, primarily a disease of the small airways. We have reported that BOS is associated with a lack of suppression of cytotoxic mediators, and pro-inflammatory cytokines, in peripheral blood T, NKT-like (particularly CD8+) and NK cells. We also showed a loss of glucocorticoid receptor (GCR) in pro-inflammatory lymphocytes following transplant. It is unknown whether these pro-inflammatory lymphocytes target the small and/or large airways in BOS...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27896523/a-cd57-ctl-degranulation-assay-effectively-identifies-familial-hemophagocytic-lymphohistiocytosis-type-3-patients
#5
Masayuki Hori, Takahiro Yasumi, Saeko Shimodera, Hirofumi Shibata, Eitaro Hiejima, Hirotsugu Oda, Kazushi Izawa, Tomoki Kawai, Masataka Ishimura, Naoko Nakano, Ryutaro Shirakawa, Ryuta Nishikomori, Hidetoshi Takada, Satoshi Morita, Hisanori Horiuchi, Osamu Ohara, Eiichi Ishii, Toshio Heike
PURPOSE: Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is a genetic disorder that results in immune dysregulation. It requires prompt and accurate diagnosis. A natural killer (NK) cell degranulation assay is often used to screen for FHL3 patients. However, we recently encountered two cases of late-onset FHL3 carrying novel UNC13D missense mutations: in these cases, the degranulation assays using freshly isolated and interleukin (IL)-2-activated NK cells yielded contradictory results...
November 28, 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/27894665/modulatory-effects-of-curcumin-on-apoptosis-and-cytotoxicity-related-molecules-in-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp-patients
#6
Asadollah Mohammadi, Bahare Fazeli, Marzieh Taheri, Amirhossein Sahebkar, Zohreh Poursina, Vida Vakili, Shadi Zamanian Yazdi, Zahra Keramati, Reza Boostani, Ian Hampson, Houshang Rafatpanah
Apoptosis is a universal cellular defense mechanism against viral infection. Curcumin, an anti-inflammatory phytochemical, induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. Here, we investigated the impact of supplementation with curcumin on the expression of a panel of apoptosis- and cytotoxicity-related genes in patients suffering from HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive demyelinating neuroinflammatory disease caused by HTLV-1 infection...
November 25, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27891129/immunological-and-translational-aspects-of-nk-cell-based-antitumor-immunotherapies
#7
REVIEW
Maxim Shevtsov, Gabriele Multhoff
Natural killer (NK) cells play a pivotal role in the first line of defense against cancer. NK cells that are deficient in CD3 and a clonal T cell receptor (TCR) can be subdivided into two major subtypes, CD56(dim)CD16(+) cytotoxic and CD56(bright)CD16(-) immunoregulatory NK cells. Cytotoxic NK cells not only directly kill tumor cells without previous stimulation by cytotoxic effector molecules, such as perforin and granzymes or via death receptor interactions, but also act as regulatory cells for the immune system by secreting cytokines and chemokines...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27872210/distribution-and-activation-of-cd8-t-cells-in-the-duodenal-mucosa-before-and-after-hiv-seroconversion
#8
Kristina Allers, Andreas Puyskens, Hans-Jörg Epple, Dirk Schürmann, Jörg Hofmann, Verena Moos, Thomas Schneider
CD8(+) T cells in the intestinal mucosa influence the HIV-associated pathogenesis, but little is known about the dynamics of mucosal CD8(+) T cell counts and activation of these cells during the course of infection. In this study, mucosal CD8(+) T cells in the duodenum were studied at different stages of HIV infection, starting from the seronegative phase. In seronegative acute HIV infection, CD8(+) T cell counts increased in the epithelium, but not in the lamina propria. Infiltration of the lamina propria by peripherally expanded CD8(+) T cells was observed after seroconversion...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27871261/quantitative-characterization-of-t-cell-repertoire-and-biomarkers-in-kidney-transplant-rejection
#9
Houda Alachkar, Martin Mutonga, Taigo Kato, Sowjanya Kalluri, Yoichi Kakuta, Motohide Uemura, Ryoichi Imamura, Norio Nonomura, Vikas Vujjini, Sami Alasfar, Hamid Rabb, Yusuke Nakamura, Nada Alachkar
BACKGROUND: T-cell-mediated rejection (TCMR) remains a major cause of kidney allograft failure. The characterization of T-cell repertoire in different immunological disorders has emerged recently as a novel tool with significant implications. We herein sought to characterize T-cell repertoire using next generation sequencing to diagnose TCMR. METHODS: In this prospective study, we analyzed samples from 50 kidney transplant recipients. We collected blood and kidney transplant biopsy samples at sequential time points before and post transplant...
November 21, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27861156/an-nk-cell-line-hank-expressing-high-levels-of-granzyme-and-engineered-to-express-the-high-affinity-cd16-allele
#10
Caroline Jochems, James W Hodge, Massimo Fantini, Rika Fujii, Y Maurice Morillon Ii, John W Greiner, Michelle R Padget, Sarah R Tritsch, Kwong Yok Tsang, Kerry S Campbell, Hans Klingemann, Laurent Boissel, Shahrooz Rabizadeh, Patrick Soon-Shiong, Jeffrey Schlom
Natural killer (NK) cells are known to play a role in mediating innate immunity, in enhancing adaptive immune responses, and have been implicated in mediating anti-tumor responses via antibody-dependent cell-mediated cytotoxicity (ADCC) by reactivity of CD16 with the Fc region of human IgG1 antibodies. The NK-92 cell line, derived from a lymphoma patient, has previously been well characterized and adoptive transfer of irradiated NK-92 cells has demonstrated safety and shown preliminary evidence of clinical benefit in cancer patients...
November 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27858143/erratum-to-novel-immunoregulatory-role-of-perforin-positive-dendritic-cells
#11
Ran Orgad, Bar Nathansohn-Levi, Sivan Kagan, Yael Zlotnikov Klionsky, Yair Reisner
No abstract text is available yet for this article.
November 17, 2016: Seminars in Immunopathology
https://www.readbyqxmd.com/read/27857713/killing-of-microbes-and-cancer-by-the-immune-system-with-three-mammalian-pore-forming-killer-proteins
#12
REVIEW
Eckhard R Podack, George P Munson
Immunology is the science of biological warfare between the defenses of our immune systems and offensive pathogenic microbes and cancers. Over the course of his scientific career, Eckhard R. Podack made several seminal discoveries that elucidated key aspects of this warfare at a molecular level. When Eckhard joined the complement laboratory of Müller-Eberhard in 1974, he was fascinated by two questions: (1) what is the molecular mechanism by which complement kills invasive bacteria? and (2) which one of the complement components is the killer molecule? Eckhard's quest to answer these questions would lead to the discovery C9 and later, two additional pore-forming killer molecules of the immune system...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27856754/mouse-model-for-acute-epstein-barr-virus-infection
#13
Tristan Wirtz, Timm Weber, Sven Kracker, Thomas Sommermann, Klaus Rajewsky, Tomoharu Yasuda
Epstein-Barr Virus (EBV) infects human B cells and drives them into continuous proliferation. Two key viral factors in this process are the latent membrane proteins LMP1 and LMP2A, which mimic constitutively activated CD40 receptor and B-cell receptor signaling, respectively. EBV-infected B cells elicit a powerful T-cell response that clears the infected B cells and leads to life-long immunity. Insufficient immune surveillance of EBV-infected B cells causes life-threatening lymphoproliferative disorders, including mostly germinal center (GC)-derived B-cell lymphomas...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27854511/a-negative-feedback-loop-between-autophagy-and-immune-responses-in-mycobacterium-leprae-infection
#14
Yuelong Ma, Li Zhang, Jie Lu, Tiejun Shui, Jia Chen, Jun Yang, Joanna Yuan, Yeqiang Liu, Degang Yang
The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level...
November 17, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27850984/1348-immune-memory-alters-cytokine-storm-and-treatment-response-in-the-perforin-deficient-model-of-hlh
#15
Matthew Taylor, Edward Behrens
No abstract text is available yet for this article.
December 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/27849169/mechanisms-of-acute-toxicity-in-nkg2d-chimeric-antigen-receptor-t-cell-treated-mice
#16
Marie-Louise Sentman, Joana M Murad, W James Cook, Ming-Ru Wu, Jake Reder, Susanne H Baumeister, Glenn Dranoff, Michael W Fanger, Charles L Sentman
Targeting cancer through the use of effector T cells bearing chimeric Ag receptors (CARs) leads to elimination of tumors in animals and patients, but recognition of normal cells or excessive activation can result in significant toxicity and even death. CAR T cells based on modified NKG2D receptors are effective against many types of tumors, and their efficacy is mediated through direct cytotoxicity and cytokine production. Under certain conditions, their ligands can be expressed on nontumor cells, so a better understanding of the potential off-tumor activity of these NKG2D CAR T cells is needed...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27847359/human-asymptomatic-epitopes-identified-from-the-herpes-simplex-virus-tegument-protein-vp13-14-ul47-preferentially-recall-polyfunctional-effector-memory-cd44highcd62llowcd8-tem-cells-and-protect-humanized-hla-a-02-01-transgenic-mice-against-ocular-herpes
#17
Ruchi Srivastava, Arif A Khan, Sumit Garg, Sabrina A Syed, Julie N Furness, Hawa Vahed, Tiffany Pham, Howard T Yu, Anthony B Nesburn, Lbachir BenMohamed
: The herpes simplex virus type 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8(+) T cells play a role in the "natural protection" seen in asymptomatic (ASYMP) individuals (have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 693 amino acids sequence of VP13/14 protein...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27846431/increased-tim3-cd8-t-cells-in-myelodysplastic-syndrome-patients-displayed-less-perforin-and-granzyme-b-secretion-and-higher-cd95-expression
#18
Jinglian Tao, Lijuan Li, Yingshuai Wang, Rong Fu, Huaquan Wang, Zonghong Shao
T cell immunoglobulin and mucin domain 3(TIM3) is a negative regulator of cellular immunity and it is highly expressed on CD8+T cells in persistent viral infection and cancer setting as report. However, how TIM3 expressed on CD8+T cells in myelodysplastic syndrome (MDS), that is a malignant disorder, has not been clarified. Here, decreased CD8+T cells, less IFN-γ secretion in CD8+T cells and increased TIM3 on CD8+T cells had been seen. Increased TIM3+CD8+T cells with lower perforin and granzyme B expression and higher CD95 expression in MDS patients had been observed...
November 2, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27835944/optimization-and-evaluation-of-luminex-performance-with-supernatants-of-antigen-stimulated-peripheral-blood-mononuclear-cells
#19
Mathieu Surenaud, Céline Manier, Laura Richert, Rodolphe Thiébaut, Yves Levy, Sophie Hue, Christine Lacabaratz
BACKGROUND: The Luminex bead-based multiplex assay is useful for quantifying immune mediators such as cytokines and chemokines. Cross-comparisons of reagents for this technique from different suppliers have already been performed using serum or plasma but rarely with supernatants collected from antigen-stimulated peripheral blood mononuclear cells (PBMC). Here, we first describe an optimization protocol for cell culture including quantity of cells and culture duration to obtain reproducible cytokine and chemokine quantifications...
November 11, 2016: BMC Immunology
https://www.readbyqxmd.com/read/27827375/predominance-of-weakly-cytotoxic-t-bet-low-eomes-neg-cd8-t-cells-in-human-gastrointestinal-mucosa-implications-for-hiv-infection
#20
B E Kiniry, A Ganesh, J W Critchfield, P W Hunt, F M Hecht, M Somsouk, S G Deeks, B L Shacklett
The gastrointestinal mucosa is an important site of HIV acquisition, viral replication, and pathogenesis. Immune cells in mucosal tissues frequently differ in phenotype and function from their non-mucosal counterparts. Although perforin-mediated cytotoxicity as measured in blood is a recognized correlate of HIV immune control, its role in gastrointestinal tissues is unknown. We sought to elucidate the cytotoxic features of rectal mucosal CD8(+) T-cells in HIV infected and uninfected subjects. Perforin expression and lytic capacity were significantly reduced in rectal CD8(+) T-cells compared with their blood counterparts, regardless of HIV clinical status; granzyme B (GrzB) was reduced to a lesser extent...
November 9, 2016: Mucosal Immunology
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