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Claire E Gustafson, Qian Qi, Jessica Hutter-Saunders, Sheena Gupta, Rohit Jadhav, Evan Newell, Holden Maecker, Cornelia M Weyand, Jörg J Goronzy
Aging is associated with an increased susceptibility to infection and a failure to control latent viruses thought to be driven, at least in part, by alterations in CD8 T cell function. The aging T cell repertoire is characterized by an accumulation of effector CD8 T cells, many of which express the negative regulatory receptor CD85j. To define the biological significance of CD85j expression on CD8 T cells and to address the question whether presence of CD85j in older individuals is beneficial or detrimental for immune function, we examined the specific attributes of CD8 T cells expressing CD85j as well as the functional role of CD85j in antigen-specific CD8 T cell responses during immune aging...
2017: Frontiers in Immunology
Jérôme Rey, Cyril Fauriat, Eloïse Kochbati, Florence Orlanducci, Aude Charbonnier, Evelyne D'Incan, Pascale Andre, François Romagne, Bernadette Barbarat, Norbert Vey, Daniel Olive
NK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML (n = 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated...
2017: Frontiers in Immunology
Sareetha Kailayangiri, Bianca Altvater, Christian Spurny, Silke Jamitzky, Sonja Schelhaas, Andreas H Jacobs, Constanze Wiek, Katharina Roellecke, Helmut Hanenberg, Wolfgang Hartmann, Heinz Wiendl, Susann Pankratz, Jutta Meltzer, Nicole Farwick, Lea Greune, Maike Fluegge, Claudia Rossig
Activated and in vitro expanded natural killer (NK) cells have substantial cytotoxicity against many tumor cells, but their in vivo efficacy to eliminate solid cancers is limited. Here, we used chimeric antigen receptors (CARs) to enhance the activity of NK cells against Ewing sarcomas (EwS) in a tumor antigen-specific manner. Expression of CARs directed against the ganglioside antigen GD2 in activated NK cells increased their responses to GD2+ allogeneic EwS cells in vitro and overcame resistance of individual cell lines to NK cell lysis...
2017: Oncoimmunology
Yamila Sol Rocca, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Luisina Bruno, Sergio Rivero, Eduardo Huertas, Fernando Sánchez Loria, Alejandro Pairola, Anne Caignard, José Mordoh, Estrella Mariel Levy
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression...
2016: Frontiers in Immunology
Uriel Y Moreno-Nieves, Céline Didier, Yves Lévy, Françoise Barré-Sinoussi, Daniel Scott-Algara
Natural killer (NK) cells are the major antiviral effector population of the innate immune system. We previously found that S100A9 is a novel ligand of the receptor CD85j and that S100A9 tetramers enhance the anti-HIV activity of NK cells. Also, we found that dendritic cells (DCs) infected by the HIV vaccine candidate, MVAHIV, prime NK cells to specifically control HIV infection in autologous CD4(+) T cells. In this study, we analyzed whether stimulation of NK cells by S100A9 tetramers prior to the priming by MVAHIV-infected DCs modulates the subsequent anti-HIV activity of NK cells...
2015: Frontiers in Immunology
Elisavet Serti, Xenia Chepa-Lotrea, Yun Ju Kim, Meghan Keane, Nancy Fryzek, T Jake Liang, Marc Ghany, Barbara Rehermann
BACKGROUND & AIMS: Chronic hepatitis C virus infection activates an intrahepatic immune response, leading to increased expression of interferon (IFN)-stimulated genes and activation of natural killer (NK) cells-the most prevalent innate immune cell in the liver. We investigated whether the elimination of hepatitis C virus with direct-acting antiviral normalizes expression of IFN-stimulated genes and NK cell function. METHODS: We used multicolor flow cytometry to analyze NK cells from the liver and blood of 13 HCV-infected patients who did not respond to treatment with pegylated interferon and ribavirin...
July 2015: Gastroenterology
María P Roberti, Estefanía P Juliá, Yamila S Rocca, Mora Amat, Alicia I Bravo, José Loza, Federico Coló, Carlos M Loza, Verónica Fabiano, Mercedes Maino, Ariel Podhorzer, Leonardo Fainboim, María M Barrio, José Mordoh, Estrella M Levy
Clinical studies suggest that triple negative breast cancer (TNBC) patients with epidermal growth factor receptor (EGFR)-expressing tumors could benefit from therapy with Cetuximab, which targets EGFR. NK cells are the primary effectors of antibody (Ab)-dependent cell-mediated cytotoxicity (ADCC) and thus play a role in Ab-based therapies. We have previously described diminished levels of Cetuximab-mediated ADCC in vitro in patients with advanced breast cancer. Here, we investigated the potential causes of this NK-cell functional deficiency...
May 2015: European Journal of Immunology
Vincent Arnold, Jean-Saville Cummings, Uriel Y Moreno-Nieves, Céline Didier, Adrien Gilbert, Françoise Barré-Sinoussi, Daniel Scott-Algara
BACKGROUND: The reportedly broad expression of CD85j across different immune cell types suggests an importance for this molecule in the human immune system. Previous reports have shown that this receptor interacts with several HLA class-I molecules, as well as with some viral proteins. We have demonstrated that the subset of CD85j + Natural Killer (NK) cells efficiently controls human immunodeficiency virus type 1 (HIV-1) replication in monocyte-derived dendritic cells (MDDC) in vitro and this led us to hypothesize that the CD85j + NK cell-mediated anti-HIV activity in MDDC is specifically dependent on the interaction between the CD85j receptor and unknown non-HLA class-I ligand(s)...
2013: Retrovirology
Paulina Własiuk, Waldemar Tomczak, Małgorzata Zając, Anna Dmoszyńska, Krzysztof Giannopoulos
Suppressed immune status facilitates immune escape mechanisms that allow chronic lymphocytic leukemia cells to proliferate and expand. The expression of HLA-G could effectively inhibit the immune response. In immune response inhibitory signals follow activation of immune system which might be occur during bacterial or viral infection in CLL patients. In the current study we characterized two components of immune system, inhibitory molecule HLA-G with its receptor - CD85j and Toll-like receptor 9. The material was obtained from 41 CLL patients and 41 HV with similar median age...
December 2013: Human Immunology
Francesco Marras, Elena Nicco, Federica Bozzano, Antonio Di Biagio, Chiara Dentone, Emanuele Pontali, Silvia Boni, Maurizio Setti, Giancarlo Orofino, Eugenio Mantia, Valentina Bartolacci, Francesca Bisio, Agostino Riva, Roberto Biassoni, Lorenzo Moretta, Andrea De Maria
Control of HIV replication in elite controller (EC) and long-term nonprogressor (LTNP) patients has been associated with efficient CD8(+)cytotoxic T-lymphocyte function. However, innate immunity may play a role in HIV control. We studied the expression of natural cytotoxicity receptors (NKp46, NKp30, and NKp44) and their induction over a short time frame (2-4 d) on activation of natural killer (NK) cells in 31 HIV controller patients (15 ECs, 16 LTNPs). In EC/LTNP, induction of NKp46 expression was normal but short (2 d), and NKp30 was induced to lower levels vs...
July 16, 2013: Proceedings of the National Academy of Sciences of the United States of America
Adriana Monsiváis-Urenda, Diana Gómez-Martin, Karina Santana-de-Anda, José Cruz-Martínez, Jorge Alcocer-Varela, Roberto González-Amaro
Dendritic cells (DCs) play an important role in inducing immune tolerance. Inhibitory receptors, such as ILT2/CD85j, are involved in the tolerogenic effect of DCs and previous studies have indicated the important role of these receptors on the pathogenesis of autoimmune diseases. The aim of this study was to evaluate the expression and function of ILT2 in DCs from SLE patients. Peripheral blood from fifty patients with SLE and 38 healthy volunteers was obtained. ILT2 expression was assessed by flow cytometry...
September 2013: Human Immunology
Nicholas L Li, Li Fu, Hannes Uchtenhagen, Adnane Achour, Deborah N Burshtyn
Leukocyte Ig-like receptor (LIR) 1 (CD85j/ILT2/LILRB1) is an inhibitory receptor with broad specificity for MHC class I (MHC-I) and the human CMV MHC-I homologue UL18. LIR-1 can inhibit NK cells through the conventional interaction with MHC-I expressed on a target cell (in trans) but the nature and the effects of LIR-1 interactions with MHC-I in cis are not well understood. Here we show that MHC-I expressed in cis has an impact on the detection of LIR-1 with various antibodies. We found the cis interaction alters recognition by only one of two antibodies known to block functional trans recognition by LIR-1 on NK cells...
April 2013: European Journal of Immunology
Alba Grifoni, Carla Montesano, Paolo Palma, Alfredo Salerno, Vittorio Colizzi, Massimo Amicosante
HLA class I molecules play a role in the regulation of innate immune response. Therefore, the interaction of HLA class I molecules with different activating and inhibitory receptors leads to balancing the immune response. Among the different family of receptors, NK receptors KIR3DL1/S1 and LIR1, play a major role. Aim of this study was to evaluate the role of amino acid polymorphic positions of HLA class I molecules interacting with NK receptors in HIV progression. In order to minimize the influence of viral variability, a cohort of children with a nosocomial monophyletic HIV-1 infection from the Benghazi Children Hospital has been evaluated...
April 2013: Molecular Immunology
Silke Heidenreich, Christine Zu Eulenburg, York Hildebrandt, Thomas Stübig, Heidi Sierich, Anita Badbaran, Thomas H Eiermann, Thomas M C Binder, Nicolaus Kröger
The role of different receptors in natural-killer- (NK-) cell-mediated cytotoxicity against multiple myeloma (MM) cells is unknown. We investigated if an enhancement of NK-cell-mediated cytotoxicity against MM could be reached by blocking of the inhibitory leukocyte immunoglobulin-like receptor 1 (LIR-1). Our investigations revealed high levels of LIR-1 expression not only on the NK cell line NK-92, but also on myeloma cells (MOLP-8, RPMI8226) as well as on a lymphoblastoid cell line (LBCL; IM-9). Subsequent cytotoxicity assays were designed to show the isolated effects of LIR-1 blocking on either the effector or the tumor side to rule out receptor-receptor interactions...
2012: Clinical & Developmental Immunology
Venkata Ramana Rao Parasa, Rajasekaran Sikhamani, Alamelu Raja
BACKGROUND: NK cells express several specialized receptors through which they recognize and discriminate virally-infected/tumor cells efficiently from healthy cells and kill them. This ability to lyse is regulated by an array of inhibitory or activating receptors. The present study investigated the frequency of various NK receptors expressed by NK cell subsets from HIV-infected TB patients. The effect of IL-15+IL-12 stimulation on the expression of NK receptors was also studied. METHODOLOGY/PRINCIPAL FINDINGS: The study included 15 individuals each from normal healthy subjects, pulmonary tuberculosis patients, HIV-infected individuals and patients with HIV and tuberculosis co-infection...
2012: PloS One
Virginie Prod'homme, Peter Tomasec, Charles Cunningham, Marius K Lemberg, Richard J Stanton, Brian P McSharry, Eddie C Y Wang, Simone Cuff, Bruno Martoglio, Andrew J Davison, Véronique M Braud, Gavin W G Wilkinson
Human CMV (HCMV)-encoded NK cell-evasion functions include an MHC class I homolog (UL18) with high affinity for the leukocyte inhibitory receptor-1 (CD85j, ILT2, or LILRB1) and a signal peptide (SP(UL40)) that acts by upregulating cell surface expression of HLA-E. Detailed characterization of SP(UL40) revealed that the N-terminal 14 aa residues bestowed TAP-independent upregulation of HLA-E, whereas C region sequences delayed processing of SP(UL40) by a signal peptide peptidase-type intramembrane protease. Most significantly, the consensus HLA-E-binding epitope within SP(UL40) was shown to promote cell surface expression of both HLA-E and gpUL18...
March 15, 2012: Journal of Immunology: Official Journal of the American Association of Immunologists
Romain Marlin, Marion Duriez, Nadia Berkane, Claire de Truchis, Yoann Madec, Marie-Anne Rey-Cuille, Jean-Saville Cummings, Claude Cannou, Heloise Quillay, Françoise Barré-Sinoussi, Marie-Thérèse Nugeyre, Elisabeth Menu
During the first trimester of human pregnancy, Natural Killer (NK) cells of the maternal uterine mucosa (e.g. decidua) have a unique phenotype and are involved in crucial physiological processes during pregnancy. We investigated whether modifications of the NK receptor repertoire occur during the first trimester of pregnancy. We found significantly decreased expression of KIR2DL1/S1 and KIR2DL2/L3/S2 receptors, NKp30 and NKp44 activatory receptors, and the CD85j (ILT-2) inhibitory receptor. We also observed significantly increased expression of the NKG2D activatory receptor at the decidual NK cell surface...
2012: PloS One
José Peña, Mario Frías, Laura Castro-Orgaz, Rafael González, Felipe García, Teresa Gallart, Jose María Gatell, Montserrat Plana
Changes in natural killer (NK) cells according to their phenotype and expression of certain regulatory receptors were analyzed in a double-blind, controlled study of antiretroviral therapy (ART)-untreated HIV-seropositive patients, who had been vaccinated with monocyte-derived dendritic cells pulsed with inactivated HIV-1 autologous virus. This work extends other recently published studies of the same group of HIV-1(+) vaccinated patients, which demonstrated that the viral load significantly decreases and correlates inversely with an increase in HIV-specific T-cell responses in vaccinated patients, but not in controls who received placebo...
February 2012: Viral Immunology
Federica Bozzano, Antonino Picciotto, Paola Costa, Francesco Marras, Valentina Fazio, Ivan Hirsch, Daniel Olive, Lorenzo Moretta, Andrea De Maria
Specific NK cell killer inhibitory receptor (KIR):HLA haplotype combinations have been associated with successful clearance of acute and chronic HCV infection. Whether an imbalance of activating NK cell receptors also contributes to the outcome of treatment of chronic HCV infection, however, is not known. We studied peripheral NK cell phenotype and function in 28 chronically viraemic HCV genotype I treatment-naïve patients who underwent treatment with pegylated IFN-α and ribavirin. At baseline, chronically infected patients with sustained virological response (SVR) had reduced CD56(bright) CD16(+/-) cell populations, increased CD56(dull) CD16(+) NK cell proportions, and lower expression of NKp30, DNAM-1, and CD85j...
October 2011: European Journal of Immunology
Lesly Doníz-Padilla, Amalia E Paniagua, Pilar Sandoval-Correa, Adriana Monsiváis-Urenda, Susanna Leskela, Mónica Marazuela, Roberto González-Amaro
OBJECTIVE: Autoimmune thyroid disease (AITD) is characterized by different defects in immunoregulatory mechanisms. The immunoglobulin-like transcript receptor 2 (ILT2) or leukocyte Ig-like receptor 1 (LIRB1/CD85j) exerts an important immunoregulatory role. We hypothesized that the lymphocytes from AITD patients have a diminished expression and function of ILT2. The aim of this study was to investigate the expression and function of ILT2 in lymphocytes from patients with AITD. DESIGN AND METHODS: In this study, 18 patients with Hashimoto's thyroiditis (HT), 20 with Graves' disease, and 26 healthy controls were studied...
July 2011: European Journal of Endocrinology
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