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NK cell memory

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https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#1
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28794018/redefining-memory-building-the-case-for-adaptive-nk-cells
#2
Silke Paust, Catherine A Blish, R Keith Reeves
Classically, natural killer (NK) cells have been defined by nonspecific innate killing of virus-infected and tumor cells. However, burgeoning evidence suggests that the functional repertoire of NK cells is far more diverse than has been previously appreciated, thus raising the possibility that there could be unexpected functional specialization and even adaptive capabilities among NK cell subpopulations. Some of the first evidence that NK cells respond in an antigen-specific fashion came from experiments revealing that subpopulations of murine NK cells could respond to a specific MCMV protein, and that in the absence of T and B cells, murine NK cells also mediated adaptive immune responses to a secondary challenge with specific haptens...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28791125/nkg2c-memory-like-nk-cells-contribute-to-the-control-of-hiv-viremia-during-primary-infection-optiprim-anrs-147
#3
Françoise Gondois-Rey, Antoine Chéret, Samuel Granjeaud, Françoise Mallet, Ghislain Bidaut, Camille Lécuroux, Mickaël Ploquin, Michaela Müller-Trutwin, Christine Rouzioux, Véronique Avettand-Fenoël, Alessandro Moretta, Gilles Pialoux, Cécile Goujard, Laurence Meyer, Daniel Olive
Natural-killer (NK) cells are important immune effectors during a viral infection. Latent CMV infection is widely spread and was demonstrated to shape the NK cell repertoire through the NKG2C receptor. An expansion of NKG2C(+) NK cells has been reported during primary HIV infection (PHI), but their role is not known. We previously found a correlation between the maturation state of the NK cell compartment and a lower viral load by studying patients from the ANRS 147 Optiprim trial. We investigated here extensively the NKG2C(+) NK cells at the time of PHI and its evolution after 3 months of early antiretroviral therapy (combination antiretroviral therapy (cART))...
July 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28781750/natural-killer-cells-in-herpesvirus-infections
#4
REVIEW
Christian Münz, Obinna Chijioke
Natural killer (NK) cells are potent innate cytotoxic lymphocytes for the destruction of infected and transformed cells. Although they were originally considered to be ready-made assassins after their hematopoietic development, it has recently become clear that their activity is regulated by mechanisms such as repertoire composition, licensing, priming, and adaptive memory-like differentiation. Some of these mechanisms are influenced by infectious disease agents, including herpesviruses. In this review, we will compare expansion, stimulation, and effector functions of NK cell populations after infections with β- and γ 1-herpesviruses because, though closely related, these pathogens seem to drive completely opposite NK cell responses...
2017: F1000Research
https://www.readbyqxmd.com/read/28780374/maternal-t-and-b-cell-engraftment-in-two-cases-of-x-linked-severe-combined-immunodeficiency-with-igg1-gammopathy
#5
Tsubasa Okano, Takuro Nishikawa, Eri Watanabe, Takashi Watanabe, Takehiro Takashima, Tzu-Wen Yeh, Motoi Yamashita, Mari Tanaka-Kubota, Satoshi Miyamoto, Noriko Mitsuiki, Masatoshi Takagi, Yoshifumi Kawano, Yoshiki Mochizuki, Kohsuke Imai, Hirokazu Kanegane, Tomohiro Morio
X-linked severe combined immunodeficiency (X-SCID), caused by defects in the common gamma chain, is typically characterized by T and NK cell defects with the presence of B cells. T cell dysfunction and impaired class-switch recombination of B cells mean that patients typically have defects in class-switched immunoglobulins (IgG, IgA, and IgE) with detectable IgM. Here, we describe two patients with X-SCID with IgG1 gammopathy, in whom we identified maternal T and B cell engraftment. Exclusively, maternal B cells were found among the IgD(-)CD27(+) class-switched memory B cells, whereas the patients' B cells remained naïve...
August 2, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28768726/cutting-edge-2b4-mediated-coinhibition-of-cd4-t-cells-underlies-mortality-in-experimental-sepsis
#6
Ching-Wen Chen, Rohit Mittal, Nathan J Klingensmith, Eileen M Burd, Cox Terhorst, Greg S Martin, Craig M Coopersmith, Mandy L Ford
Sepsis is a leading cause of death in the United States, but the mechanisms underlying sepsis-induced immune dysregulation remain poorly understood. 2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8(+) T cells that has been shown to regulate T cell function in models of viral infection and autoimmunity. In this article, we show that 2B4 signaling mediates sepsis lymphocyte dysfunction and mortality. 2B4 expression is increased on CD4(+) T cells in septic animals and human patients at early time points...
August 2, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28733665/human-intrahepatic-cd69%C3%A2-%C3%A2-cd8-t-cells-have-a-tissue-resident-memory-t-cell-phenotype-with-reduced-cytolytic-capacity
#7
Femke Stelma, Annikki de Niet, Marjan J Sinnige, Karel A van Dort, Klaas P J M van Gisbergen, Joanne Verheij, Ester M M van Leeuwen, Neeltje A Kootstra, Hendrik W Reesink
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687661/a-systems-vaccinology-approach-reveals-temporal-transcriptomic-changes-of-immune-responses-to-the-yellow-fever-17d-vaccine
#8
Jue Hou, Shuhui Wang, Manxue Jia, Dan Li, Ying Liu, Zhengpeng Li, Hong Zhu, Huifang Xu, Meiping Sun, Li Lu, Zhinan Zhou, Hong Peng, Qichen Zhang, Shihong Fu, Guodong Liang, Lena Yao, Xuesong Yu, Lindsay N Carpp, Yunda Huang, Julie McElrath, Steve Self, Yiming Shao
In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays...
July 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28680749/tumor-priming-converts-nk-cells-to-memory-like-nk-cells
#9
Marina Pal, Lisa Schwab, Anastasiya Yermakova, Emily M Mace, Rainer Claus, Ann-Christin Krahl, Jeanette Woiterski, Udo F Hartwig, Jordan S Orange, Rupert Handgretinger, Maya C André
Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28679778/combination-therapy-with-nhs-muil12-and-avelumab-anti-pd-l1-enhances-antitumor-efficacy-in-preclinical-cancer-models
#10
Chunxiao Xu, Yanping Zhang, P Alexander Rolfe, Vivian M Hernández, Wilson Guzman, Giorgio Kradjian, Bo Marelli, Guozhong Qin, Jin Qi, Hong Wang, Huakui Yu, Robert Tighe, Kin-Ming Lo, Jessie M English, Laszlo G Radvanyi, Yan Lan
To determine if combination therapy with NHS-muIL12 and the anti-PD-L1 antibody avelumab can enhance anti-tumor efficacy in preclinical models relative to monotherapies.<br /><br />Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt(-) mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28659489/transcriptional-profiling-confirms-the-therapeutic-effects-of-mast-cell-stabilization-in-a-dengue-disease-model
#11
Juliet Morrison, Abhay P S Rathore, Chinmay K Mantri, Siti A B Aman, Andrew Nishida, Ashley L St John
There are no approved therapeutics for the treatment of dengue disease despite the global prevalence of dengue virus (DENV) and its mosquito vectors. DENV infections can lead to vascular complications, hemorrhage and shock due to the ability of DENV to infect a variety of immune and non-immune cell populations. Increasingly, studies have implicated the host response as a major contributor to severe disease. Inflammatory products of various cell types, including responding T cells, mast cells (MCs) and infected monocytes can contribute to immune pathology...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28659311/memory-t-cells-expressing-an-nkg2d-car-efficiently-target-osteosarcoma-cells
#12
Lucía Fernández, Jean-Yves Metais, Adela Escudero, Maria Vela, Jaime Valentín, Isabel Vallcorba, Alejandra Leivas, Juan Torres, Antonio Valeri, Ana Patiño-García, Joaquín Martínez-López, Wing Leung, Antonio Pérez-Martínez
NKG2D ligands (NKG2DL) are expressed on various tumor types and immunosuppressive cells within tumor microenvironments, providing suitable targets for cancer therapy. Various immune cells express NKG2D receptors, including natural killer (NK) cells and CD8+ T cells. Interactions between NKG2DL and NKG2D receptors are essential for NK cell elimination of osteosarcoma tumor initiating cells. In this report, we used NKG2D-NKG2DL interactions to optimize an immunotherapeutic strategy against osteosarcoma. We evaluated in vitro and in vivo the safety and cytotoxic capacity against osteosarcoma cells of CD45RA- memory T cells expressing an NKG2D-4-1BB-CD3z chimeric antigen receptor (CAR)...
June 28, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28638735/maternal-microchimerism-is-prevalent-in-cord-blood-in-memory-t-cells-and-other-cell-subsets-and-persists-post-transplant
#13
Sami B Kanaan, Hilary S Gammill, Whitney E Harrington, Stephen C De Rosa, Philip A Stevenson, Alexandra M Forsyth, Judy Allen, Emma Cousin, Koen van Besien, Colleen S Delaney, J Lee Nelson
Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-vs.-leukemia (GVL) are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this GVL benefit. We assayed MMc directly and hypothesized benefit accrues from CB maternal T cells. MMc was quantified in 51 CBs and, within memory T, naïve T, B, NK cells, and monocytes in 27 CBs...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28611767/natural-killer-defective-maturation-is-associated-with-adverse-clinical-outcome-in-patients-with-acute-myeloid-leukemia
#14
Anne-Sophie Chretien, Cyril Fauriat, Florence Orlanducci, Claire Galseran, Jerome Rey, Gaelle Bouvier Borg, Emmanuel Gautherot, Samuel Granjeaud, Jean-François Hamel-Broza, Clemence Demerle, Norbert Ifrah, Catherine Lacombe, Pascale Cornillet-Lefebvre, Jacques Delaunay, Antoine Toubert, Emilie Gregori, Herve Luche, Marie Malissen, Christine Arnoulet, Jacques A Nunes, Norbert Vey, Daniel Olive
Accumulating evidence highlights natural killer (NK) cell parameters as potential prognostic factors in cancer patients, which provides a strong rationale for developing therapeutic strategies aiming at restoring NK cell. However, reaching this point warrants better characterization of tumor-induced NK cell alterations. Our group recently reported heterogeneous NK maturation in acute myeloid leukemia (AML) patients. However, the clinical significance of such observations remained to be assessed on a larger cohort of patients...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28588205/human-uterine-lymphocytes-acquire-a-more-experienced-and-tolerogenic-phenotype-during-pregnancy
#15
Dorien Feyaerts, Marilen Benner, Bram van Cranenbroek, Olivier W H van der Heijden, Irma Joosten, Renate G van der Molen
Pregnancy requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Despite increasing knowledge, data is lacking on the transition of pre-pregnancy endometrial lymphocytes to a pregnancy state. Here, we immunophenotyped lymphocytes from endometrium (MMC), term decidua parietalis (DPMC), and PBMC for direct comparison. We found that the immune cell composition of MMC and DPMC clearly differ from each other, with less NK-cells, and more NKT-cells and T-cells in DPMC...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28586095/cmv-drives-the-expansion-of-highly-functional-memory-t-cells-expressing-nk-cell-receptors-in-renal-transplant-recipients
#16
Nandini Makwana, Bree Foley, Sonia Fernandez, Silvia Lee, Ashley Irish, Hanspeter Pircher, Patricia Price
Cytomegalovirus (CMV) is a common opportunistic infection encountered in renal transplant recipients (RTRs) and may be reactivated without symptoms at any time post-transplant. We describe how active and latent CMV affect T-cell subsets in RTRs who are stable on maintenance therapy. T-cell responses to CMV were assessed in RTRs (n = 54) >2 years post-transplant, and healthy controls (n = 38). Seven RTRs had CMV DNA detectable in plasma. CMV antibody and DNA aligned with increased proportions of CD8(+) T cells and reduced CD4/CD8 ratios...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28582858/alterations-in-the-peripheral-immune-system-in-dementia
#17
Mandy Busse, Enrico Michler, Franz von Hoff, Henrik Dobrowolny, Roland Hartig, Thomas Frodl, Stefan Busse
Alterations in the immune response that result in inflammation might play a role in the pathology of dementias. In order to analyze changes of the peripheral immune system associated with different types of dementias, we determined several innate and adaptive cell populations in whole blood using flow cytometry. We included patients with Alzheimer's disease (AD; n = 60), vascular dementia (VaD; n = 20), and frontotemporal dementia (FTD; n = 12) at the time point of diagnosis and 24 age-matched neuropsychiatric healthy persons...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28574833/new-interleukin-15-superagonist-il-15sa-significantly-enhances-graft-versus-tumor-activity
#18
Cavan P Bailey, Tulin Budak-Alpdogan, Christopher T Sauter, Michelle M Panis, Cihangir Buyukgoz, Emily K Jeng, Hing C Wong, Neal Flomenberg, Onder Alpdogan
Interleukin-15 (IL-15) is a potent cytokine that increases CD8+ T and NK cell numbers and function in experimental models. However, obstacles remain in using IL-15 therapeutically, specifically its low potency and short in vivo half-life. To help overcome this, a new IL-15 superagonist complex comprised of an IL-15N72D mutation and IL-15RαSu/Fc fusion (IL-15SA, also known as ALT-803) was developed. IL-15SA exhibits a significantly longer serum half-life and increased in vivo activity against various tumors...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28572802/chimeric-antigen-receptor-engineered-nk-92-cells-an-off-the-shelf-cellular-therapeutic-for-targeted-elimination-of-cancer-cells-and-induction-of-protective-antitumor-immunity
#19
Congcong Zhang, Pranav Oberoi, Sarah Oelsner, Anja Waldmann, Aline Lindner, Torsten Tonn, Winfried S Wels
Significant progress has been made in recent years toward realizing the potential of natural killer (NK) cells for cancer immunotherapy. NK cells can respond rapidly to transformed and stressed cells and have the intrinsic potential to extravasate and reach their targets in almost all body tissues. In addition to donor-derived primary NK cells, also the established NK cell line NK-92 is being developed for adoptive immunotherapy, and general safety of infusion of irradiated NK-92 cells has been established in phase I clinical trials with clinical responses observed in some of the cancer patients treated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28557197/impaired-immune-function-in-children-and-adults-with-fanconi-anemia
#20
Kasiani C Myers, Sharon Sauter, Xue Zhang, Jacob J Bleesing, Stella M Davies, Susanne I Wells, Parinda A Mehta, Ashish Kumar, Daniel Marmer, Rebecca Marsh, Darron Brown, Melinda Butsch Kovacic
BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder characterized by genome instability, bone marrow failure, and cancer predisposition. Previously, small studies have reported heterogeneous immune dysfunction in FA. PROCEDURE: We performed a detailed immunologic assessment in a large FA cohort who have not undergone bone marrow transplantation or developed malignancies. Comprehensive quantitative and functional immunologic assessment of 29 FA individuals was compared to healthy age-matched controls...
May 30, 2017: Pediatric Blood & Cancer
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