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https://www.readbyqxmd.com/read/28077266/asp0028-in-combination-with-suboptimal-dose-of-tacrolimus-in-cynomolgus-monkey-renal-transplantation-model
#1
Hao Dun, Lijun Song, Anlun Ma, Yanxin Hu, Lin Zeng, Jieying Bai, Guangzhou Zhang, Liangyan Zhang, Kumi Koide, Yohei Okada, Kaori Hanaoka, Rie Yamamoto, Jun Hirose, Tatsuaki Morokata, Pierre Daloze, Huifang Chen
FTY720, a S1P-receptor modulator, has shown to be effective in several transplant and autoimmune disease models, via modulating lymphocyte homing into secondary lymphoid organs (SLOs), and thereby reducing these cells in peripheral blood. ASP0028, a newly developed S1P1/S1P5-selective agonist, presented comparable efficacy to FTY720 and wider safety margins than FTY720. In this study, we assessed the efficacy and safety of ASP0028 co-administered with suboptimal-dose of tacrolimus in the Cynomolgus monkey renal transplantation model...
January 7, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28076903/slamf7-engagement-restores-defective-effector-cd8-t-cells-activity-in-response-to-foreign-antigens-in-systemic-lupus-erythematosus
#2
Denis Comte, Maria P Karampetsou, Nobuya Yoshida, Katalin Kis-Toth, Vasileios C Kyttaris, George C Tsokos
OBJECTIVE: Effector CD8+ T cell function is impaired in SLE and associated with compromised ability to fight infections. SLAMF7 engagement has been shown to enhance NK cell degranulation. Thus, we characterized the expression and function of SLAMF7 on CD8+ T cells subsets isolated from peripheral blood of SLE patients and healthy subjects. METHODS: CD8+ T cell subset distribution, SLAMF7 expression and cytolytic enzyme expression (perforin, GzmA, GzmB) were monitored on cells isolated from SLE patients and healthy controls by flow cytometry...
January 11, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28063015/innate-immunity-against-legionella-pneumophila-during-pulmonary-infections-in-mice
#3
REVIEW
Bonggoo Park, Gayoung Park, Jiyoung Kim, Seon Ah Lim, Kyung-Mi Lee
Legionella pneumophila is an etiological agent of the severe pneumonia known as Legionnaires' disease (LD). This gram-negative bacterium is thought to replicate naturally in various freshwater amoebae, but also replicates in human alveolar macrophages. Inside host cells, legionella induce the production of non-endosomal replicative phagosomes by injecting effector proteins into the cytosol. Innate immune responses are first line defenses against legionella during early phases of infection, and distinguish between legionella and host cells using germline-encoded pattern recognition receptors such as Toll-like receptors , NOD-like receptors, and RIG-I-like receptors, which sense pathogen-associated molecular patterns that are absent in host cells...
January 6, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28062694/effective-combination-of-innate-and-adaptive-immunotherapeutic-approaches-in-a-mouse-melanoma-model
#4
Alexander L Rakhmilevich, Mildred Felder, Lauren Lever, Jacob Slowinski, Kayla Rasmussen, Anna Hoefges, Tyler J Van De Voort, Hans Loibner, Alan J Korman, Stephen D Gillies, Paul M Sondel
Most cancer immunotherapies include activation of either innate or adaptive immune responses. We hypothesized that the combined activation of both innate and adaptive immunity will result in better antitumor efficacy. We have previously shown the synergy of an agonistic anti-CD40 mAb (anti-CD40) and CpG-oligodeoxynucleotides in activating macrophages to induce tumor cell killing in mice. Separately, we have shown that a direct intratumoral injection of immunocytokine (IC), an anti-GD2 Ab linked to IL-2, can activate T and NK cells resulting in antitumor effects...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28055112/identification-of-human-memory-like-nk-cells
#5
Elena I Kovalenko, Maria A Streltsova, Leonid M Kanevskiy, Sophia A Erokhina, William G Telford
Our understanding of NK biology is increased dramatically, a product of improved flow-cytometric techniques for analyzing these cells. NK cells undergo significant changes in repertoire during differentiation. A repeating stimulus, such as a cytomegalovirus infection, may result in accumulation of certain types of highly differentiated NK cells designated as memory-like, or adaptive NK cells. Adaptive NK cells are capable of rapid expansion and effective response to the recall stimulus. These cells differ significantly from conventional NK cells both functionally and phenotypically...
January 5, 2017: Current Protocols in Cytometry
https://www.readbyqxmd.com/read/28031340/il-15-enables-septic-shock-by-maintaining-nk-cell-integrity-and-function
#6
Yin Guo, Liming Luan, Naeem K Patil, Jingbin Wang, Julia K Bohannon, Whitney Rabacal, Benjamin A Fensterheim, Antonio Hernandez, Edward R Sherwood
Interleukin 15 is essential for the development and differentiation of NK and memory CD8(+) (mCD8(+)) T cells. Our laboratory previously showed that NK and CD8(+) T lymphocytes facilitate the pathobiology of septic shock. However, factors that regulate NK and CD8(+) T lymphocyte functions during sepsis are not well characterized. We hypothesized that IL-15 promotes the pathogenesis of sepsis by maintaining NK and mCD8(+) T cell integrity. To test our hypothesis, the pathogenesis of sepsis was assessed in IL-15-deficient (IL-15 knockout, KO) mice...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28031334/respiratory-influenza-virus-infection-induces-memory-like-liver-nk-cells-in-mice
#7
Tingting Li, Jian Wang, Yanshi Wang, Yongyan Chen, Haiming Wei, Rui Sun, Zhigang Tian
Although NK cells are classified as innate immune cells, recent studies have demonstrated the transformation of NK cells into long-lived memory cells that contribute to secondary immune responses in certain mouse models. However, whether NK cells mount an Ag-specific memory response to acute influenza virus infection has not yet been examined. Here, we show that, consistent with previous studies, lung NK cells play an important role in controlling viral proliferation after primary influenza virus infection...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28008151/tonsillar-cd56brightnkg2a-nk-cells-restrict-primary-epstein-barr-virus-infection-in-b-cells-via-ifn-%C3%AE
#8
Aurelia Jud, Monika Kotur, Christoph Berger, Claudine Gysin, David Nadal, Anna Lünemann
Natural killer (NK) cells constitute the first line of defense against viruses and cancers cells. Epstein-Barr virus (EBV) was the first human virus to be directly implicated in carcinogenesis, and EBV infection is associated with a broad spectrum of B cell lymphomas. How NK cells restrict EBV-associated oncogenesis is not understood. Here, we investigated the efficacies and mechanisms of distinct NK cell subsets from tonsils, the portal of entry of EBV, in limiting EBV infection in naïve, germinal center-associated and memory B cells...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27999289/characterization-of-the-microenvironment-of-nodular-lymphocyte-predominant-hodgkin-lymphoma
#9
Lydia Visser, Rui Wu, Bea Rutgers, Arjan Diepstra, Anke van den Berg
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by a low percentage of neoplastic lymphocyte predominant (LP) cells in a background of lymphocytes. The goal of this study is to characterize the microenvironment in NLPHL. Ten NLPHL cases and seven reactive lymph nodes (RLN) were analyzed by flow cytometry for the main immune cells and multiple specific subpopulations. To discriminate between cells in or outside the tumor cell area, we used CD26. We observed significantly lower levels of CD20+ B-cells and CD56+ NK cells and higher levels of CD4+ T-cells in NLPHL in comparison to RLN...
December 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27984782/nk-cells-in-host-responses-to-viral-infections
#10
REVIEW
Viola C Lam, Lewis L Lanier
Natural killer (NK) cells are cytotoxic innate lymphocytes that play an important role in viral clearance. NK cell responses to viral infections were originally believed to be non-specific and lacked immune memory recall responses. It is now appreciated that NK cell responses to viral infections can be specific and in some cases memory recall responses are established. Increasing evidence also illuminates the complexity of NK cell interactions with both innate and adaptive immune cells. Here, we summarize the evidence for NK cell-specific memory responses to viral infections and the intricate reciprocal interactions between NK cells and other immune cells that dictate their activation and effector functions...
December 13, 2016: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27980216/characterization-of-ifn%C3%AE-producing-natural-killer-cells-induced-by-cytomegalovirus-reactivation-after-haploidentical-hematopoietic-stem-cell-transplantation
#11
Fengyan Jin, Hai Lin, Sujun Gao, Hengxiang Wang, Hongmin Yan, Jinglong Guo, Zheng Hu, Chunhui Jin, Yongqi Wang, Zhidong Wang, Yangzhi Zhao, Yu Liu, Xiaoli Zheng, Yehui Tan, Wei Li, Yun Dai, Yanping Yang
During human cytomegalovirus (CMV) infection after umbilical cord blood or HLA-matched hematopoietic stem cell transplantation (HSCT), a population of NKG2C-expressing natural killer (NK) cells expand and persist. The expanded NK cells express high levels of inhibitory killer immunoglobulin-like receptors (KIR) specific for self-HLA and potently produce IFNγ. However, it remains unknown whether similar events would occur after haploidentical HSCT (haplo-HSCT). Here, we demonstrated that IFNγ-producing NK cells were expanded in haplo-HSCT patients with CMV reactivation...
December 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27974453/epigenetic-networks-regulate-the-transcriptional-program-in-memory-and-terminally-differentiated-cd8-t-cells
#12
Ramon M Rodriguez, Beatriz Suarez-Alvarez, José L Lavín, David Mosén-Ansorena, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Ana M Aransay, Carlos Lopez-Larrea
Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8(+) T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells...
December 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27974365/nk-cells-require-antigen-specific-memory-cd4-t-cells-to-mediate-superior-effector-functions-during-hsv-2-recall-responses-in-vitro
#13
Branson Chen, Amanda J Lee, Marianne V Chew, Ali A Ashkar
Natural killer (NK) cells have an important role in mounting protective innate responses against genital herpes simplex virus type 2 (HSV-2) infections. However their role as effectors in adaptive immune responses against HSV-2 is unclear. Here, we demonstrate that NK cells from C57BL/6 mice in an ex vivo splenocyte culture produce significantly more interferon γ (IFN-γ) upon re-exposure to HSV-2 antigens in a mouse model of genital HSV-2 immunization. We find that naïve NK cells do not require any prior stimulation or priming to be activated to produce IFN-γ...
December 14, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27942037/time-of-initiating-enzyme-replacement-therapy-affects-immune-abnormalities-and-disease-severity-in-patients-with-gaucher-disease
#14
Renuka Pudi Limgala, Chidima Ioanou, Matthew Plassmeyer, Mark Ryherd, Lina Kozhaya, Lauren Austin, Cem Abidoglu, Derya Unutmaz, Oral Alpan, Ozlem Goker-Alpan
Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT...
2016: PloS One
https://www.readbyqxmd.com/read/27924822/il-21-dependent-expansion-of-memory-like-nk-cells-enhances-protective-immune-responses-against-mycobacterium-tuberculosis
#15
S Venkatasubramanian, S Cheekatla, P Paidipally, D Tripathi, E Welch, A R Tvinnereim, R Nurieva, R Vankayalapati
Natural killer (NK) cells are traditionally considered as innate cells, but recent studies suggest that NK cells can distinguish antigens, and that memory NK cells expand and protect against viral pathogens. Limited information is available about the mechanisms involved in memory-like NK cell expansion, and their role in bacterial infections and vaccine-induced protective immune responses. In the current study, using a mouse model of tuberculosis (TB) infection, we found that interferon-gamma producing CD3-NKp46+CD27+KLRG1+ memory-like NK cells develop during Bacille Calmette-Guérin vaccination, expand, and provide protection against challenge with Mycobacterium tuberculosis (M...
December 7, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27911410/experimental-infection-with-listeria-monocytogenes-as-a-model-for-studying-host-interferon-%C3%AE-responses
#16
Jeeyoon Jennifer Ahn, Thirumahal Selvanantham, Monan Angela Zhang, Thierry Mallevaey, Shannon E Dunn
L. monocytogenes is a gram-positive bacterium that is a cause of food borne disease in humans. Experimental infection of mice with this pathogen has been highly informative on the role of innate and adaptive immune cells and specific cytokines in host immunity against intracellular pathogens. Production of IFN-γ by innate cells during sublethal infection with L. monocytogenes is important for activating macrophages and early control of the pathogen(1-3). In addition, IFN-γ production by adaptive memory lymphocytes is important for priming the activation of innate cells upon reinfection(4)...
November 16, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27902485/impacts-of-cigarette-smoking-on-immune-responsiveness-up-and-down-or-upside-down
#17
REVIEW
Feifei Qiu, Chun-Ling Liang, Huazhen Liu, Yu-Qun Zeng, Shaozhen Hou, Song Huang, Xiaoping Lai, Zhenhua Dai
Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27896283/a-potential-founder-variant-in-carmil2-rltpr-in-three-norwegian-families-with-warts-molluscum-contagiosum-and-t-cell-dysfunction
#18
Hanne S Sorte, Liv T Osnes, Børre Fevang, Pål Aukrust, Hans C Erichsen, Paul H Backe, Tore G Abrahamsen, Ole B Kittang, Torstein Øverland, Shalini N Jhangiani, Donna M Muzny, Magnus D Vigeland, Pubudu Samarakoon, Tomasz Gambin, Zeynep H C Akdemir, Richard A Gibbs, Olaug K Rødningen, Robert Lyle, James R Lupski, Asbjørg Stray-Pedersen
BACKGROUND: Four patients from three Norwegian families presented with a common skin phenotype of warts, molluscum contagiosum, and dermatitis since early childhood, and various other immunological features. Warts are a common manifestation of human papilloma virus (HPV), but when they are overwhelming, disseminated and/or persistent, and presenting together with other immunological features, a primary immunodeficiency disease (PIDD) may be suspected. METHODS AND RESULTS: The four patients were exome sequenced as part of a larger study for detecting genetic causes of primary immunodeficiencies...
November 2016: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/27894857/cytokine-induced-memory-like-differentiation-enhances-unlicensed-natural-killer-cell-antileukemia-and-fc%C3%AE-riiia-triggered-responses
#19
Julia A Wagner, Melissa M Berrien-Elliott, Maximillian Rosario, Jeffrey W Leong, Brea A Jewell, Timothy Schappe, Sara Abdel-Latif, Todd A Fehniger
Cytokine-induced memory-like natural killer (NK) cells differentiate after short-term preactivation with IL-12, IL-15, and IL-18 and display enhanced effector function in response to cytokines or tumor targets for weeks after the initial preactivation. Conventional NK cell function depends on a licensing signal, classically delivered by an inhibitory receptor engaging its cognate MHC class I ligand. How licensing status integrates with cytokine-induced memory-like NK cell responses is unknown. We investigated this interaction using killer cell immunoglobulin-like receptor- and HLA-genotyped primary human NK cells...
November 25, 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27892871/phenotypic-modulation-of-porcine-cd14-monocytes-natural-killer-natural-killer-t-cells-and-cd8%C3%AE-%C3%AE-t-cell-subsets-by-an-antibody-derived-killer-peptide-kp
#20
Luca Ferrari, Paolo Borghetti, Giulia Ferrarini, Elena De Angelis, Elena Canelli, Giulia Ogno, Alessia Catella, Tecla Ciociola, Walter Magliani, Paolo Martelli
An engineered killer peptide (KP) based on a recombinant anti-idiotypic antibody representing the functional image of a yeast killer toxin (KT) was demonstrated to mediate antimicrobial effects against fungi and viruses. KP binds to murine dendritic cells and macrophages and up-regulate co-receptor expression, thus sustaining CD4+ lymphocyte activation. No immunological data are available in domestic animals thus KP-induced immunomodulation was evaluated in porcine monocyte and lymphocyte subsets. PBMC from healthy adult pigs were stimulated with KP or a scramble peptide (SP), or kept unstimulated for 24, 48 and 72h, and subsequently analyzed by flow cytometry...
December 2016: Research in Veterinary Science
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