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Nathalie Rouas-Freiss, Joel LeMaoult, Jérôme Verine, Diana Tronik-Le Roux, Stéphane Culine, Christophe Hennequin, François Desgrandchamps, Edgardo D Carosella
The establishment and maintenance of anti-tumor immune responses are the objectives of cancer immunotherapy. Despite recent promising advances, the effectiveness of these approaches has been limited by the multiple immunosuppressive mechanisms developed by tumors (checkpoint). The aim of the present study was to demonstrate intratumor heterogeneity at the levels of immune escape strategies and tumor-host relationships. We focused on well-known checkpoints such as PD1/PDL1 and on a new checkpoint involving HLA-G and its receptors ILT2/ILT4...
2017: Oncoimmunology
Maria T Cencioni, Roberta Magliozzi, Richard Nicholas, Rehiana Ali, Omar Malik, Richard Reynolds, Giovanna Borsellino, Luca Battistini, Paolo Muraro
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the CNS of patients with Multiple Sclerosis (pwMS) as a possible cause of disease. In this study, we have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 pwMS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death-1 (PD-1) and human inhibitor receptor Ig-like transcript 2 (ILT2)...
August 2, 2017: Immunology
Izabela Nowak, Karolina Wilczyńska, Jacek R Wilczyński, Andrzej Malinowski, Paweł Radwan, Michał Radwan, Piotr Kuśnierczyk
Reproductive failure in humans is a very important social and economic problem, because nowadays women decide to conceive later in life and delay motherhood. Unfortunately, with increasing age they have less chance for natural fertilization and maintenance of pregnancy. Many of them need assisted reproductive technology. Approximately 10% of women after in vitro fertilization-embryo transfers experience recurrent implantation failure (RIF). Multiple factors may contribute to RIF, including oocyte and sperm quality, parental chromosomal anomalies, genetic or metabolic abnormalities of the embryo, poor uterine receptivity, immunological disturbances in the implantation site, and some gynecologic pathologies such as endometriosis, uterine fibroids, hydrosalpinx and endometrial polyps...
May 18, 2017: Archivum Immunologiae et Therapiae Experimentalis
Erick C Castelli, Petroula Gerasimou, Michelle A Paz, Jaqueline Ramalho, Iane O P Porto, Thálitta H A Lima, Andréia S Souza, Luciana C Veiga-Castelli, Cristhianna V A Collares, Eduardo A Donadi, Celso T Mendes-Junior, Paul Costeas
The HLA-G molecule presents immunomodulatory properties that might inhibit immune responses when interacting with specific Natural Killer and T cell receptors, such as KIR2DL4, ILT2 and ILT4. Thus, HLA-G might influence the outcome of situations in which fine immune system modulation is required, such as autoimmune diseases, transplants, cancer and pregnancy. The majority of the studies regarding the HLA-G gene variability so far was restricted to a specific gene segment (i.e., promoter, coding or 3' untranslated region), and was performed by using Sanger sequencing and probabilistic models to infer haplotypes...
March 2017: Molecular Immunology
Chen Chen, Jun Liang, Genhong Yao, Haifeng Chen, Bingyu Shi, Zhuoya Zhang, Cheng Zhao, Huayong Zhang, Lingyun Sun
BACKGROUND: Soluble human leukocyte antigen-G (sHLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of T regulatory cells (Treg). Mesenchymal stem cells (MSCs) transplantation alleviates disease progression in systemic lupus erythematosus (SLE) patients. However, the underlying mechanisms are largely unknown. OBJECTIVES: To explore whether sHLA-G is involved in upregulating effects of MSCs on Treg, which contributes to therapeutic effects of MSCs transplantation in SLE...
March 2017: International Immunopharmacology
Guillermo Juárez-Vega, Velia Rangel-Ramírez, Adriana Monsiváis-Urenda, Perla Niño-Moreno, Christian Garcia-Sepúlveda, Daniel E Noyola, Roberto González-Amaro
Human cytomegalovirus (HCMV) infection in children and young adults has been associated with changes in the innate immune system. We herein analyzed the possible effect of very long term HCMV infection on the expression of several NK cell receptors. Ninety HCMV-seropositive individuals were included and classified as young adults (n=30), elderly (n=30) and very elderly subjects (n=30). A peripheral blood sample was obtained and the expression of NK cell receptors (NKG2A, NKG2C, ILT2, CD161, KIR2DL1, KIR3DL1, and KIR3DL2) by NK and other lymphocyte subsets was assessed by flow cytometry...
March 2017: Human Immunology
L L Bi, Y Gao, Y J Sun, X R Kong, X Y He, X H Ma, W H Zhang, L Xiao, B Y Shi
Objective: To study the expression of membrane HLA-G (mHLA-G) and the receptor immunoglobulin-like transcript 2(ILT2) on lymphocyte and find their association with rejection and cytomegalovirus (CMV) infection after renal transplantation. Methods: A total of 88 cases of renal transplant recipients for the first time from February 2014 to February 2016 were studied in this work. Recipients can be divided into rejection group (n=12) and stable renal function group (n=41) according to whether rejection occurred...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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
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