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H Eguchi, A Maeda, P C Lo, R Matsuura, E L Esquivel, M Asada, R Sakai, K Nakahata, T Yamamichi, S Umeda, K Deguchi, T Ueno, H Okuyama, S Miyagawa
The inhibitory function of HLA-G1, a class Ib molecule, on monocyte/macrophage-mediated cytotoxicity was examined. The expression of inhibitory receptors that interact with HLA-G, immunoglobulin-like transcript 2 (ILT2), ILT4, and KIR2DL4 (CD158d) on in vitro-generated macrophages obtained from peripheral blood mononuclear cells and the phorbol 12-myristate 13-acetate (PMA)-activated THP-1 cells were examined by flow cytometry. cDNAs of HLA-G1, HLA-G3, HLA-E, and human β2-microglobulin were prepared, transfected into pig endothelial cells (PECs), and macrophage- and the THP-1 cell-mediated PEC cytolysis was then assessed...
May 2016: Transplantation Proceedings
Christine Pasero, Gwenaëlle Gravis, Mathilde Guerin, Samuel Granjeaud, Jeanne Thomassin-Piana, Palma Rocchi, Maria Paciencia-Gros, Flora Poizat, Mélanie Bentobji, Francine Azario-Cheillan, Jochen Walz, Naji Salem, Serge Brunelle, Alessandro Moretta, Daniel Olive
The field of immunotherapy for solid tumors, such as prostate cancer, has been recently focusing on therapies that can counter tumor-mediated immunosuppression. Precise quantification and characterization of the immune infiltrates in tumors is crucial to improve treatment efficacy. Natural killer (NK) cells, major components of the antitumor immune system, have never been isolated from prostate tumors, despite their suspected role in disease progression. Here, we examined the frequency, phenotype, and functions of NK cells infiltrating control and tumor prostate tissues...
April 15, 2016: Cancer Research
Simon Jasinski-Bergner, Adi Reches, Christine Stoehr, Chiara Massa, Evamaria Gonschorek, Stefan Huettelmaier, Juliane Braun, Sven Wach, Bernd Wullich, Verena Spath, Ena Wang, Francesco M Marincola, Ofer Mandelboim, Arndt Hartmann, Barbara Seliger
The non-classical human leukocyte antigen G (HLA-G) is expressed at a high frequency in renal cell carcinoma (RCC) and is associated with a higher tumor grade and a poor clinical outcome. This might be caused by the HLA-G-mediated inhibition of the cytotoxicity of T and NK cells. Therefore a selective targeting of HLA-G might represent a powerful strategy to enhance the immunogenicity of RCC lesions. Recent studies identified a number of HLA-G-regulating microRNAs (miRs) and demonstrated an inverse expression of some of these miRs with HLA-G in RCC in vitro and in vivo...
May 3, 2016: Oncotarget
Ching-Lien Wu, Signe Goul Svendsen, Adrien Riviere, François Desgrandchamps, Edgardo D Carosella, Joël LeMaoult
Human leukocyte antigen (HLA)-G is an immune-inhibitory molecule that exerts its function via interaction with two main inhibitory receptors: ILT2 and ILT4. This interaction is considered to be an immune checkpoint. HLA-G can be found as a soluble molecule, but it is not known if its receptors can also be found as soluble molecules. In this work, we present a multiplex luminex-based assay to measure soluble ILT2 (sILT2) and soluble ILT4 (sILT4) molecules together. It is based on two antibody pairs, GHI/75 and HP-F1-PE for ILT2 and 27D6 and 42D1-PE for ILT4...
September 2016: Human Immunology
David Goldeck, Walter Maetzler, Daniela Berg, Lilly Oettinger, Graham Pawelec
Parkinson's disease (PD) is characterised by low-level systemic inflammation, which may be at least partly due to pathophysiological activation of immunity. Here, the frequencies of different types of circulating dendritic cells (DCs) with and without a pro-inflammatory phenotype were determined in PD patients and controls. A high proportion of older people is infected with cytomegalovirus (CMV), which acts as a chronic antigenic stressor that could also contribute to increased inflammation. Following this idea, we found higher frequencies of myeloid DCs with a pro-inflammatory CD16+ILT2(high) phenotype in CMV-positive PD patients than controls, suggesting the potential involvement of CMV in exacerbating PD...
January 15, 2016: Journal of Neuroimmunology
Danli Wu, Isere Kuiaste, Philippe Moreau, Edgardo Carosella, Patricia Yotnda
Several studies have demonstrated that the antitumor activities of both T and natural killer (NK) effector populations are limited by the immunosuppressive strategies of tumors. In several malignant transformations, the expression of HLA-G by tumor cells rises dramatically, rendering them strongly immunosuppressive. In this study, we postulated that the absence of HLA-G receptors would prevent the immunosuppressive effects of both soluble and membrane-bound HLA-G. Thus, we investigated the therapeutic potential of effector NK cells genetically modified to downregulate the expression of ILT2 (HLA-G receptor) on their cell surfaces...
November 10, 2015: Oncotarget
Snezana Djurisic, Lillian Skibsted, Thomas Vauvert F Hviid
PROBLEM: The prevalence of regulatory T cells and NK cells expressing activation and HLA-G receptors, and the influence of in vivo sHLA-G and mHLAG on HLA-G receptors expressed by NK cells in the uterine compartment is unclear. METHOD OF STUDY: KIR2DL4 and/or ILT2 expression on regulatory T cells and NK cells from the placental bed and peripheral blood in first trimester was assessed using flow cytometry. Expression of mHLA-G on trophoblast cells and sHLA-G in 'uterine' and peripheral blood was determined with ELISA and flow cytometry, and specific associations with expression levels of cognate receptors or activation markers on immune cells were determined...
November 2015: American Journal of Reproductive Immunology: AJRI
Daria Bortolotti, Joel LeMaoult, Claudio Trapella, Dario Di Luca, Edgardo D Carosella, Roberta Rizzo
HLA-G is a nonclassical class I human leukocyte antigen (HLA) involved in mechanisms of immune tolerance. The objective of this study was to determine whether N-(3-oxododecanoyl)-l-homoserine lactone (3O-C12-HSL), a quorum sensing molecule produced by Pseudomonas aeruginosa, could modify HLA-G expression to control the host immune response. We evaluated the ability of 3O-C12-HSL to induce HLA-G expression in primary immune cells, monocytes (U937 and THP1), and T-cell lines (Jurkat) in vitro and analyzed the cellular pathway responsible for HLA-G expression...
October 2015: Infection and Immunity
Monika Biedroń, Justyna Rybka, Tomasz Wróbel, Iwona Prajs, Rafał Poręba, Kazimierz Kuliczkowski
HLA-G is a non-classical MHC class I molecule whose suppressive activity on immune effector cells is exerted due to interactions with receptors ILT2, ILT4 and KIR2DL4. These receptors are expressed mainly on NK cells and monocytes, and their intensity of expression changes depending on HLA-G level. HLA-G plays an important role in the development of tolerance following organ transplantations and bone marrow stem cell transplantations. HLA-G also participates in the modulation of the immune response during cancerogenesis...
August 2015: Medical Oncology
Jessica Schmitt, Sigrid Eckardt, Paul G Schlegel, Anna-Leena Sirén, Valentin S Bruttel, K John McLaughlin, Jörg Wischhusen, Albrecht M Müller
Parent-of-origin imprints have been implicated in the regulation of neural differentiation and brain development. Previously we have shown that, despite the lack of a paternal genome, human parthenogenetic (PG) embryonic stem cells (hESCs) can form proliferating neural stem cells (NSCs) that are capable of differentiation into physiologically functional neurons while maintaining allele-specific expression of imprinted genes. Since biparental ("normal") hESC-derived NSCs (N NSCs) are targeted by immune cells, we characterized the immunogenicity of PG NSCs...
2015: Molecular Medicine
Laurence Amiot, Nicolas Vu, Michel Samson
The non-classical human leukocyte antigen-G (HLA-G), plays an important role in inducing tolerance, through its immunosuppressive effects on all types of immune cells. Immune tolerance is a key issue in the liver, both in liver homeostasis and in the response to liver injury or cancer. It would therefore appear likely that HLA-G plays an important role in liver diseases. Indeed, this molecule was recently shown to be produced by mast cells in the livers of patients infected with hepatitis C virus (HCV). Furthermore, the number of HLA-G-positive mast cells was significantly associated with fibrosis progression...
June 2015: Journal of Hepatology
Emilio L Esquivel, Akira Maeda, Hiroshi Eguchi, Mayumi Asada, Miku Sugiyama, Chieko Manabe, Rieko Sakai, Rei Matsuura, Kengo Nakahata, Hiroomi Okuyama, Shuji Miyagawa
BACKGROUND: Xenotransplantation is an appealing alternative to human allotransplantation because of a worldwide shortage of organs. One of the obstacles for xenografts is cellular rejection by the innate immune system, comprised of NK cells, monocytes, and macrophages. In this study the inhibitory function of HLA-G1, a MHC Ib molecule, on macrophage-mediated cytotoxicity was examined. Furthermore, this study also evaluates the suppressive effect of cytokine production by macrophages. METHODS: The expression of inhibitory receptors that interact with HLA-G1, immunoglobulin-like transcript 2 (ILT2), ILT4 and KIR2DL4 (CD158d) on in vitro generated macrophages were examined by flow cytometry...
March 2015: Transplant Immunology
Xinjing Wang, Xianghong Meng, Yue Zheng, Jing Jiang, Bingfen Yang, Yanhua Liu, Fei Zhai, Xiaoxing Cheng
The functional role of ILT2 in anti-tuberculosis immunity remains to be elucidated. In this study, we investigated expression and functions of ILT2 on NK cells during TB infection. The frequency of CD56(dim)CD16(+) NK cells that expressed ILT2 was significantly elevated in patients with active pulmonary TB as compared with tuberculin-positive healthy controls (p < 0.0001). TB patients with Mycobacterium tuberculosis smear/culture-positive result had significantly higher frequency of ILT2-expressing CD56(dim)CD16(+) NK cells than those with M...
September 2014: Tuberculosis
Archana Gopal Kulkarni, Ramesh Shivram Paranjape, Madhuri Rajeev Thakar
Natural killer (NK) cells may be important in modulating HIV replication in early course of HIV infection. The effector function of NK cells is finely tuned by a balance between signals delivered by activating and inhibitory receptors. However, the influence of expression of these receptors on the early course of HIV replication and subsequent disease progression is not explored in the context of HIV-1C infection. The expression pattern of activating (NKp46, NKp44, NKp30, NKG2D, and NKG2C) and inhibitory (CD158b, NKG2A, and ILT2) receptors was determined in 20 patients with recent HIV-1C infection within 3-7 months of acquiring HIV infection and was compared with the expression pattern in individuals with progressive (N = 12), non-progressive HIV-1C infection (LTNPs, N = 12) and healthy seronegative individuals (N = 20)...
2014: Frontiers in Immunology
Andrew Zloza, Dae Won Kim, Seunghee Kim-Schulze, Michael C Jagoda, Vladia Monsurro, Francesco M Marincola, Howard L Kaufman
BACKGROUND: Oncolytic viruses represent a novel form of cancer immunotherapy. Vaccinia viruses encoding human T cell co-stimulatory molecules have demonstrated clinical activity in phase I clinical trials in patients with advanced melanoma. However, predictive biomarkers of therapeutic response have not yet been identified. METHODS: A customized microarray was performed to identify changes in peripheral blood mononuclear cell (PBMC) gene expression upon exposure to recombinant oncolytic vaccinia viruses...
2014: Journal for Immunotherapy of Cancer
Nathalie Rouas-Freiss, Philippe Moreau, Joel LeMaoult, Edgardo D Carosella
We here review the current data on the role of HLA-G in cancer based on recent findings of an unexpected antitumor activity of HLA-G in hematological malignancies. For the past decade, HLA-G has been described as a tumor-escape mechanism favoring cancer progression, and blocking strategies have been proposed to counteract it. Aside from these numerous studies on solid tumors, recent data showed that HLA-G inhibits the proliferation of malignant B cells due to the interaction between HLA-G and its receptor ILT2, which mediates negative signaling on B cell proliferation...
2014: Journal of Immunology Research
Abderrahim Naji, Catherine Menier, Fabio Morandi, Sophie Agaugué, Guitta Maki, Elisa Ferretti, Sylvie Bruel, Vito Pistoia, Edgardo D Carosella, Nathalie Rouas-Freiss
Inhibition of B cells constitutes a rational approach for treating B cell-mediated disorders. We demonstrate in this article that the engagement of the surface Ig-like transcript 2 (ILT2) inhibitory receptor with its preferential ligand HLA-G is critical to inhibit B cell functions. Indeed, ILT2-HLA-G interaction impedes both naive and memory B cell functions in vitro and in vivo. Particularly, HLA-G inhibits B cell proliferation, differentiation, and Ig secretion in both T cell-dependent and -independent models of B cell activation...
February 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Anja E Sørensen, Claus R Johnsen, Louise T Dalgaard, Peter Adler Würtzen, Bjarne Kristensen, Margit Hørup Larsen, Henrik Ullum, Ulrik Søes-Petersen, Thomas Vauvert F Hviid
BACKGROUND: TH2-biased immune responses are important in allergy pathogenesis. Mechanisms of allergen-specific immunotherapy (SIT) might include the induction of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a reduction in the number of effector cells, and skewing of the cytokine profile towards a TH1-polarized immune response. We investigated the effects of SIT on T cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been associated with allergy, on regulatory cytokine expression, and on serum allergen-specific antibody subclasses (IgE and IgG4)...
2013: International Archives of Allergy and Immunology
Letizia Lombardelli, Maryse Aguerre-Girr, Federica Logiodice, Ornela Kullolli, Ysabel Casart, Beata Polgar, Alain Berrebi, Sergio Romagnani, Enrico Maggi, Philippe Le Bouteiller, Marie-Pierre Piccinni
Successful pregnancy in humans has been associated with production of IL-4 by T cells at the feto-maternal interface. Soluble HLA-G5 produced by trophoblasts potentially controls the decidual T cell cytokine profile. We studied the effect of HLA-G5 on the cytokine profile of purified human macrophages and Ag-specific T cells in vitro. We demonstrated that HLA-G5 increased production of IL-12 by purified peripheral blood macrophages. Although IL-12 production by macrophages is known to induce IFN-γ production by CD4(+) T cells, HLA-G5 increased production of IL-4 but not IFN-γ by CD4(+) T cells after Ag presentation by macrophages...
October 1, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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