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NK cell memory

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https://www.readbyqxmd.com/read/29440505/cutting-edge-divergent-requirement-of-t-box-transcription-factors-in-effector-and-memory-nk-cells
#1
Sharline Madera, Clair D Geary, Colleen M Lau, Olga Pikovskaya, Steven L Reiner, Joseph C Sun
The T-box transcription factors T-bet and Eomesodermin (Eomes) instruct discrete stages in NK cell development. However, their role in the immune response of mature NK cells against pathogens remains unexplored. We used an inducible deletion system to elucidate the cell-intrinsic role of T-bet and Eomes in mature NK cells during the course of mouse CMV infection. We show both T-bet and Eomes to be necessary for the expansion of virus-specific NK cells, with T-bet upregulation induced by IL-12 signaling and STAT4 binding to a conserved enhancer region upstream of the Tbx21 loci...
February 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29435021/long-lasting-memory-of-cellular-immunity-in-a-chronic-myeloid-leukemia-patient-maintains-molecular-response-5-after-cessation-of-dasatinib
#2
Tatsuro Jo, Kazuhiro Noguchi, Shizuka Hayashi, Sadaharu Irie, Risa Hayase, Haruna Shioya, Youhei Kaneko, Kensuke Horio, Jun Taguchi
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29423731/hiv-persistence-in-adipose-tissue-reservoirs
#3
REVIEW
Jacob Couturier, Dorothy E Lewis
PURPOSE OF REVIEW: The purpose of this review is to examine the evidence describing adipose tissue as a reservoir for HIV-1 and how this often expansive anatomic compartment contributes to HIV persistence. RECENT FINDINGS: Memory CD4 T cells and macrophages, the major host cells for HIV, accumulate in adipose tissue during HIV/SIV infection of humans and rhesus macaques. Whereas HIV and SIV proviral DNA is detectable in CD4 T cells of multiple fat depots in virtually all infected humans and monkeys examined, viral RNA is less frequently detected, and infected macrophages may be less prevalent in adipose tissue...
February 9, 2018: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/29401667/infectious-agents-as-stimuli-of-trained-innate-immunity
#4
REVIEW
Paulina Rusek, Mateusz Wala, Magdalena Druszczyńska, Marek Fol
The discoveries made over the past few years have modified the current immunological paradigm. It turns out that innate immunity cells can mount some kind of immunological memory, similar to that observed in the acquired immunity and corresponding to the defense mechanisms of lower organisms, which increases their resistance to reinfection. This phenomenon is termed trained innate immunity. It is based on epigenetic changes in innate immune cells (monocytes/macrophages, NK cells) after their stimulation with various infectious or non-infectious agents...
February 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29400704/functions-of-nkg2d-in-cd8-t-cells-an-opportunity-for-immunotherapy
#5
REVIEW
Kushal Prajapati, Cynthia Perez, Lourdes Beatriz Plaza Rojas, Brianna Burke, Jose A Guevara-Patino
Natural killer group 2 member D (NKG2D) is a type II transmembrane receptor. NKG2D is present on NK cells in both mice and humans, whereas it is constitutively expressed on CD8+ T cells in humans but only expressed upon T-cell activation in mice. NKG2D is a promiscuous receptor that recognizes stress-induced surface ligands. In NK cells, NKG2D signaling is sufficient to unleash the killing response; in CD8+ T cells, this requires concurrent activation of the T-cell receptor (TCR). In this case, the function of NKG2D is to authenticate the recognition of a stressed target and enhance TCR signaling...
February 5, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29372476/identification-of-candidate-biomarkers-associated-with-response-to-vedolizumab-in-inflammatory-bowel-disease
#6
Elisa K Boden, Donna M Shows, Michael V Chiorean, James D Lord
BACKGROUND/AIMS: Vedolizumab is an anti-α4β7 monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). This exploratory study aimed to identify biomarkers associated with vedolizumab response. METHODS: Twenty-six IBD patients (15 with Crohn's, 11 with ulcerative or indeterminate colitis) initiating vedolizumab at a single center between 2014 and 2016 underwent sampling of serum and peripheral blood mononuclear cells (PBMCs) before and during vedolizumab therapy...
January 25, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29367461/cd122-blockade-restores-immunological-tolerance-in-autoimmune-type-1-diabetes-via-multiple-mechanisms
#7
Xiaomei Yuan, Yi Dong, Naoya Tsurushita, J Yun Tso, Wenxian Fu
Signaling through IL-2/IL-15Rβ (CD122) is essential for the differentiation and function of T cells and NK cells. A mAb against CD122 has been implicated to suppress autoimmune type 1 diabetes (T1D) development in animal models. However, the mechanisms remain poorly understood. We find that in vivo administration of an anti-CD122 mAb (CD122 blockade) restores immune tolerance in nonobese diabetic (NOD) mice via multiple mechanisms. First, CD122 blockade selectively ablates pathogenic NK cells and memory phenotype CD8+ T cells from pancreatic islets...
January 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29363172/bcg-vaccination-drives-accumulation-and-effector-function-of-innate-lymphoid-cells-in-murine-lungs
#8
Pia Steigler, Naomi J Daniels, Tim R McCulloch, Brin M Ryder, Sarah K Sandford, Joanna R Kirman
The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB, however fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to anti-mycobacterial immunity. To that end, innate cells may be involved in the protective response...
January 9, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29358179/strategies-to-activate-nk-cells-to-prevent-relapse-and-induce-remission-following-hematopoietic-stem-cell-transplantation
#9
Sarah Cooley, Peter Parham, Jeffrey S Miller
Natural Killer (NK) cells are lymphocytes of innate immunity that respond to virus infected and tumor cells. After allogeneic transplantation, NK cells are the first reconstituting lymphocytes, but are dysfunctional. Manipulating this first wave of lymphocytes could be instrumental in reducing the 40% relapse rate following transplantation with reduced intensity conditioning. NK cells express numerous activating and inhibitory receptors. Some recognize classical or non-classical HLA class I ligands, others recognize class I-like ligands or unrelated ligands...
January 22, 2018: Blood
https://www.readbyqxmd.com/read/29355919/origins-of-natural-killer-cell-memory-special-creation-or-adaptive-evolution
#10
REVIEW
Kayla A Holder, Emilie M Comeau, Michael D Grant
The few initial formative studies describing non-specific and apparently spontaneous activity of natural killer (NK) cells have since multiplied into thousands of scientific reports defining their unique capacities and means of regulation. Characterization of the array of receptors that govern NK cell education and activation revealed an unexpected relationship with the major histocompatibility molecules that NK cells originally became well known for ignoring. Proceeding true to form, NK cells continue to upend archetypal understanding of their ever expanding capabilities...
January 21, 2018: Immunology
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#11
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29282719/il-12-il-18-preactivated-donor-nk-cells-enhance-gvl-effects-and-mitigate-gvhd-after-allogeneic-hematopoietic-stem-cell-transplantation
#12
Yuan Song, Bo Hu, Yonghao Liu, Ziqi Jin, Yinsheng Zhang, Dandan Lin, Ying Zhu, Lei Lei, Huanle Gong, Yu Mei, Huey Yee Teo, Depei Wu, Haiyan Liu
Adoptive transfer of donor NK cells has the potential of mediating graft-versus-leukemia (GVL) effect while suppressing acute graft-versus-host-disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these beneficial effects are limited by the transient function of adoptively transferred NK cells. Previous studies demonstrate that cytokine-induced memory-like NK cells that are preactivated by IL-12, IL-15, and IL-18 have enhanced effector functions and long life span in vivo...
December 27, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29247515/intrahepatic-and-peripheral-blood-phenotypes-of-nk-and-t-cells-differential-surface-expression-of-kir-receptors
#13
Ariel Podhorzer, Andrés Machicote, Santiago Belen, Leandro Lauferman, Oscar Imventarza, Silvina Montal, Sebastián Marciano, Omar Galdame, Luis G Podesta, Leonardo Fainboim
Deep characterization of the frequencies, phenotypes and functionalities of liver and peripheral blood NK, NKT and T cells from healthy individuals is an essential step to further interpret changes in liver diseases. These data indicate that CCR7, a chemokine essential for cell migration through lymphoid organs, is almost absent in liver NK and T cells. CD56bright NK cells, which represent half of liver NK cells, showed lower expression of the inhibitory molecule NKG2A and an increased frequency of the activatory marker NKp44...
December 16, 2017: Immunology
https://www.readbyqxmd.com/read/29236750/identification-of-gad65-aa-114-122-reactive-memory-like-nk-cells-in-newly-diagnosed-type-1-diabetic-patients-by-hla-class-i-pentamers
#14
Valentina Perri, Elena Gianchecchi, Loredana Cifaldi, Marsha Pellegrino, Ezio Giorda, Marco Andreani, Marco Cappa, Alessandra Fierabracci
Type 1 diabetes is an autoimmune disease, in which pancreatic β cells are destroyed by autoreactive T cells in genetically predisposed individuals. Serum beta cell autoantibody specificities have represented the mainstay for classifying diabetes as autoimmune-mediated and for stratifying risk in first-degree relatives. In recent years, approaches were attempted to solve the difficult issue of detecting rare antigen-specific autoreactive T cells and their significance to etiopathogenesis such as the use of the MHC multimer technology...
2017: PloS One
https://www.readbyqxmd.com/read/29222089/core-binding-factor-%C3%AE-and-runx-transcription-factors-promote-adaptive-natural-killer-cell-responses
#15
Moritz Rapp, Colleen M Lau, Nicholas M Adams, Orr-El Weizman, Timothy E O'Sullivan, Clair D Geary, Joseph C Sun
Natural killer (NK) cells are innate lymphocytes that have features of adaptive immunity such as clonal expansion and generation of long-lived memory. Interleukin-12 (IL-12) signaling through its downstream transcription factor signal transducer and activator of transcription 4 (STAT4) is required for the generation of memory NK cells after expansion. We identify gene loci that are highly enriched for STAT4 binding using chromatin immunoprecipitation sequencing for STAT4 and the permissive histone mark H3K4me3 in activated NK cells...
December 8, 2017: Science Immunology
https://www.readbyqxmd.com/read/29209568/phenotype-and-tissue-distribution-of-cd28h-immune-cell-subsets
#16
Joel Crespo, Linda Vatan, Tomasz Maj, Rebecca Liu, Ilona Kryczek, Weiping Zou
CD28H is a newly discovered co-receptor of the human B7 family. CD28H interacts with its ligand B7-H5 and regulates T cell response. Here we showed that CD28H was not expressed on granulocytes, monocytes, myeloid dendritic cells (MDCs), and B cells, but constitutively expressed with moderate levels on memory T cells and with high levels on naïve T cells, innate lymphoid cells (ILCs), natural killer (NK) cells, and plasmacytoid dendritic cells (PDCs) in human peripheral blood. Similar CD28H+ cell profile existed in secondary lymphoid organs and pathological tissues including multiple types of cancers...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29194419/the-interplay-between-natural-killer-cells-and-human-herpesvirus-6
#17
REVIEW
Eva Eliassen, Dario Di Luca, Roberta Rizzo, Isabel Barao
Human Herpesvirus 6 (HHV-6) is a set of two closely related herpes viruses known as HHV-6A and HHV-6B. Both are lymphotropic viruses that establish latency in the host. The ability to evade the immune responses of effector cells is likely a major factor contributing to the development of a persistent HHV-6A/B (collectively termed HHV-6) infection. Natural killer (NK) cells are lymphocytes that, along with neutrophils and monocytes/macrophages, participate in the critical innate immune response during viral infections, but can also mediate the antigen-specific memory responses generally associated with adaptive immunity...
December 1, 2017: Viruses
https://www.readbyqxmd.com/read/29190907/profile-of-differentially-expressed-toll-like-receptor-signaling-genes-in-the-natural-killer-cells-of-patients-with-s%C3%A3-zary-syndrome
#18
Kelly C G ManfrereC, Marina P Torrealba, Denis R Miyashiro, Nátalli Z Pereira, Fabio S Y Yoshikawa, Luana de M Oliveira, Jade Cury-Martins, Alberto J S Duarte, José A Sanches, Maria N Sato
Sézary syndrome (SS), an aggressive and leukemic form of cutaneous T-cell lymphoma, usually results in shortened survival. Improving innate immunity in SS by targeting natural killer (NK) cells with Toll-like receptor (TLR) agonists could be an interesting modulatory strategy. We evaluated the NK cell populations in SS patients assessing activating and inhibitory receptors expression and profiled the differential expression of TLR signaling pathway genes in unstimulated NK cells and after TLR7/8 stimulation...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29180124/nk-cells-in-autoimmune-diseases-linking-innate-and-adaptive-immune-responses
#19
REVIEW
Elena Gianchecchi, Domenico Vittorio Delfino, Alessandra Fierabracci
The pathogenesis of autoimmunity remains to be fully elucidated, although the contribution of genetic and environmental factors is generally recognized. Despite autoimmune conditions are principally due to T and B lymphocytes, NK cells also appear to play a role in the promotion and/or maintenance of altered adaptive immune responses or in peripheral tolerance mechanisms. Although NK cells are components of the innate immune system, they shows characteristics of the adaptive immune system, such as the expansion of pathogen-specific cells, the generation of long-lasting "memory" cells able to persist upon cognate antigen encounter, and the possibility to induce an increased secondary recall response to re-challenge...
February 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/29178433/triptolide-inhibits-donor-specific-antibody-production-and-attenuates-mixed-antibody-mediated-renal-allograft-injury
#20
Daqiang Zhao, Siwen Li, Tao Liao, Yuan Wei, Mingyu Liu, Fei Han, Zihuan Luo, Xiaonan Liu, Qiquan Sun
Donor-specific antibodies (DSAs) are major mediators of renal allograft injury, and strategies to inhibit DSAs are important in promoting long-term graft survival. Triptolide exhibits a wide spectrum of antiinflammatory and immunosuppressive activities, and in autoimmune diseases it inhibits autoantibody levels. In this study, we investigated the suppressive role of triptolide in the generation of DSAs in transplant recipients. We found that triptolide treatment of skin allograft recipients in mice significantly suppressed the development of circulating anti-donor-specific IgG and effectively alleviated DSA-mediated renal allograft injury, which led to prolonged allograft survival...
November 27, 2017: American Journal of Transplantation
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