TY - JOUR AU - Gémes, Nikolett AU - Balog, József Ágoston AU - Neuperger, Patricia AU - Schlegl, Erzsébet AU - Barta, Imre AU - Fillinger, János AU - Antus, Balázs AU - Zvara, Ágnes AU - Hegedűs, Zoltán AU - Czimmerer, Zsolt AU - Manczinger, Máté AU - Balogh, Gergő Mihály AU - Tóvári, József AU - Puskás, László AU - Szebeni, Gábor TI - Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC. JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 16 SN - 1664-3224 DO - 10.3389/fimmu.2023.1297577 UR - https://m2.mtmt.hu/api/publication/34486293 ID - 34486293 N1 - * Megosztott szerzőség AB - Tobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).Smoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4-/CD8-, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA-/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA-/CD45RO+/CD197-) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups.Our focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients.The applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Tamás AU - Mir, Mohd Yaqub AU - Stefancsik, Gergely AU - Ganbat, Gantulga AU - Askarova, Aruzhan AU - Monostori, Éva AU - Dulka, Karolina AU - Szebeni, Gábor AU - Nyúl-Tóth, Ádám AU - Csiszar, Anna AU - Légrádi, Ádám TI - Galectin-1 as a marker for microglia activation in the aging brain JF - BRAIN RESEARCH J2 - BRAIN RES VL - 1818 PY - 2023 PG - 13 SN - 0006-8993 DO - 10.1016/j.brainres.2023.148517 UR - https://m2.mtmt.hu/api/publication/34093747 ID - 34093747 N1 - Funding Agency and Grant Number: American Heart Association [GINOP-2.3.2-15-2016-00034, 142877 FK22]; National Research, Development, and Innovation Office (NKFI) , Hungary [AHA834339]; Ministry for Innovation and Technology from the National Research, Development and Innovation Fund; American Heart Association; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences; [EFOP-3.6.1-16-2016-00008]; [2020-1.1.6-JOVO-2021-00003]; [UNKP-22-5-SZTE-535]; [BO/00582/22/8] Funding text: This work was supported by a grant from EFOP-3.6.1-16-2016-00008 and GINOP-2.3.2-15-2016-00034 grants. ANyT was supported by American Heart Association (AHA834339) . (The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript) . This research was funded by the 2020-1.1.6-JOVO-2021-00003 and 142877 FK22, grant from the National Research, Development, and Innovation Office (NKFI) , Hungary. This work was supported by the UNKP-22-5-SZTE-535 New National Excellence Program (GJS) of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GJS) . AB - Microglia cells, the immune cells residing in the brain, express immune regulatory molecules that have a central role in the manifestation of age-related brain characteristics. Our hypothesis suggests that galectin-1, an anti-inflammatory member of the beta-galactoside-binding lectin family, regulates microglia and neuroinflammation in the aging brain. Through our in-silico analysis, we discovered a subcluster of microglia in the aged mouse brain that exhibited increased expression of galectin-1 mRNA. In our Western blotting experiments, we observed a decrease in galectin-1 protein content in our rat primary cortical cultures over time. Additionally, we found that the presence of lipopolysaccharide, an immune activator, significantly increased the expression of galectin-1 protein in microglial cells. Utilizing flow cytometry, we determined that a portion of the galectin-1 protein was localized on the surface of the microglial cells. As cultivation time increased, we observed a decrease in the expression of activation-coupled molecules in microglial cells, indicating cellular exhaustion. In our mixed rat primary cortical cell cultures, we noted a transition of amoeboid microglial cells labeled with OX42(CD11b/c) to a ramified, branched phenotype during extended cultivation, accompanied by a complete disappearance of galectin-1 expression. By analyzing the transcriptome of a distinct microglial subpopulation in an animal model of aging, we established a correlation between chronological aging and galectin-1 expression. Furthermore, our in vitro study demonstrated that galectin-1 expression is associated with the functional activation state of microglial cells exhibiting specific amoeboid morphological characteristics. Based on our findings, we identify galectin-1 as a marker for microglia activation in the context of aging. LA - English DB - MTMT ER - TY - JOUR AU - Neuperger, Patricia AU - Szalontai, Klára Margit AU - Gémes, Nikolett AU - Balog, József Ágoston AU - Tiszlavicz, László AU - Furák, József AU - Lázár, György ifj AU - Puskás, László AU - Szebeni, Gábor TI - Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 14 PY - 2023 PG - 14 SN - 1664-3224 DO - 10.3389/fimmu.2023.1243233 UR - https://m2.mtmt.hu/api/publication/34199166 ID - 34199166 N1 - Bolyai János Kutatási Ösztöndíj (BO/00582/22/8) Laboratory of Functional Genomics, HUN-REN Biological Research Centre, Szeged, Hungary PhD School in Biology, University of Szeged, Szeged, Hungary Csongrád County Hospital of Chest Diseases, Deszk, Hungary Department of Pathology, University of Szeged, Szeged, Hungary Department of Surgery, University of Szeged, Szeged, Hungary Avicor Ltd, Szeged, Hungary Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary CS-Smartlab Devices Ltd, Kozármisleny, Hungary Export Date: 7 November 2023 Correspondence Address: Puskás, L.G.; Laboratory of Functional Genomics, Hungary; email: laszlo@avidinbiotech.com Correspondence Address: Szebeni, G.J.; Laboratory of Functional Genomics, Hungary; email: szebeni.gabor@brc.hu Funding details: Magyar Tudományos Akadémia, MTA, BO/00582/22/8, ÚNKP-23-5 -SZTE-694 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFI Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, C1764415 Funding details: Innovációs és Technológiai Minisztérium Funding details: National Research, Development and Innovation Office Funding text 1: This research was funded by the 2020‐1.1.6‐JÖVŐ−2021‐00003 and 142877 FK22, KFI_16-1-2017-0105 grant from the National Research, Development, and Innovation Office (NKFI), Hungary. This work was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GS) and by the by the ÚNKP-23-5 -SZTE-694 New National Excellence Program of the Ministry for Innovation and Technology (GS). This manuscript was supported by the KDP-2021 Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund for NG (C1764415). AB - Introduction: The effect of platinum-based chemotherapy (Chem.) and second- or multiple- line immune checkpoint PD-1 blocking therapy by Nivolumab or Pembrolizumab (ICI) was assayed in the peripheral blood of non-small cell lung cancer (NSCLC) patients. Methods: Flow cytometry was used to detect NSCLC-related antigen binding IgG antibodies. The Luminex MagPix multiplex bead-based cytokine/chemokine detecting system was used to quantitatively measure 17 soluble markers in the plasma samples. Single-cell mass cytometry was applied for the immunophenotyping of peripheral leukocytes. Results: The incubation of patient derived plasma with human NSCLC tumor cell lines, such as A549, H1975, and H1650, detected NSCLC-specific antibodies reaching a maximum of up to 32% reactive IgG-positive NSCLC cells. The following markers were detected in significantly higher concentration in the plasma of Chem. group versus healthy non-smoker and smoker controls: BTLA, CD27, CD28, CD40, CD80, CD86, GITRL, ICOS, LAG-3, PD-1, PD-L1, and TLR-2. The following markers were detected in significantly higher concentration in the plasma of ICI group versus healthy non-smoker and smoker controls: CD27, CD28, CD40, GITRL, LAG-3, PD-1, PD-L1, and TLR-2. We showed the induction of CD69 and IL-2R on CD4+ CD25+ T-cells upon chemotherapy; the exhaustion of one CD8+ T-cell population was detected by the loss of CD127 and a decrease in CD27. CD19+CD20+, CD79B+, or activated B-cell subtypes showed CD69 increase and downregulation of BTLA, CD27, and IL-2R in NSCLC patients following chemotherapy or ICI. Discussion: Peripheral immunophenotype caused by chemotherapy or PD-1 blocking was shown in the context of advanced NSCLC. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Enikő AU - Modok, Szabolcs AU - Rónaszéki, Benedek AU - Faragó, Anna AU - Gémes, Nikolett AU - Nagy, Lajos I. AU - Hackler, László AU - Farkas, Katalin AU - Neuperger, Patricia AU - Balog, József Ágoston AU - Balog, Attila AU - Puskás, László AU - Szebeni, Gábor TI - Comparison of humoral and cellular immune responses in hematologic diseases following completed vaccination protocol with BBIBP-CorV, or AZD1222, or BNT162b2 vaccines against SARS-CoV-2 JF - FRONTIERS IN MEDICINE J2 - FRONT MED VL - 10 PY - 2023 PG - 11 SN - 2296-858X DO - 10.3389/fmed.2023.1176168 UR - https://m2.mtmt.hu/api/publication/34069256 ID - 34069256 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office (NKFI), Hungary [2020-1.1.6-JOVO-2021-00003, 142877 FK22, KFI_16-1-2017-0105]; KDP-2021 Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund [C1764415]; Jnos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00582/22/8]; Ministry of Culture and Innovation; New National Excellence Program [NTP-NFTOE-21-B-0164] Funding text: This research was funded by the 2020-1.1.6-JOEVO-2021-00003 and 142877 FK22, KFI_16-1-2017-0105 grant from the National Research, Development, and Innovation Office (NKFI), Hungary. This work was supported by the UNKP-22-5-SZTE-535 New National Excellence Program for GS, and by the KDP-2021 Program for NG (C1764415) of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund. This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GS). This manuscript was prepared with the professional support of SZTE AOK-KKA Hetenyi Geza Scholarship_5S726 (AB). This manuscript was prepared with the support of the National Young Talent Scholarship for ES (NTP-NFTOE-21-B-0164) by the Ministry of Culture and Innovation. AB - Vaccination has proven the potential to control the COVID-19 pandemic worldwide. Although recent evidence suggests a poor humoral response against SARS-CoV-2 in vaccinated hematological disease (HD) patients, data on vaccination in these patients is limited with the comparison of mRNA-based, vector-based or inactivated virus-based vaccines.MethodsForty-nine HD patients and 46 healthy controls (HCs) were enrolled who received two-doses complete vaccination with BNT162b2, or AZD1222, or BBIBP-CorV, respectively. The antibodies reactive to the receptor binding domain of spike protein of SARS-CoV-2 were assayed by Siemens ADVIA Centaur assay. The reactive cellular immunity was assayed by flow cytometry. The PBMCs were reactivated with SARS-CoV-2 antigens and the production of activation-induced markers (TNF-α, IFN-γ, CD40L) was measured in CD4+ or CD8+ T-cells ex vivo.ResultsThe anti-RBD IgG level was the highest upon BNT162b2 vaccination in HDs (1264 BAU/mL) vs. HCs (1325 BAU/mL) among the studied groups. The BBIBP-CorV vaccination in HDs (339.8 BAU/mL ***p < 0.001) and AZD1222 in HDs (669.9 BAU/mL *p < 0.05) resulted in weaker antibody response vs. BNT162b2 in HCs. The response rate of IgG production of HC vs. HD patients above the diagnostic cut-off value was 100% vs. 72% for the mRNA-based BNT162b2 vaccine; 93% vs. 56% for the vector-based AZD1222, or 69% vs. 33% for the inactivated vaccine BBIBP-CorV, respectively. Cases that underwent the anti-CD20 therapy resulted in significantly weaker (**p < 0.01) anti-RBD IgG level (302 BAU/mL) than without CD20 blocking in the HD group (928 BAU/mL). The response rates of CD4+ TNF-α+, CD4+ IFN-γ+, or CD4+ CD40L+ cases were lower in HDs vs. HCs in all vaccine groups. However, the BBIBP-CorV vaccine resulted the highest CD4+ TNF-α and CD4+ IFN-γ+ T-cell mediated immunity in the HD group.ConclusionWe have demonstrated a significant weaker overall response to vaccines in the immunologically impaired HD population vs. HCs regardless of vaccine type. Although, the humoral immune activity against SARS-CoV-2 can be highly evoked by mRNA-based BNT162b2 vaccination compared to vector-based AZD1222 vaccine, or inactivated virus vaccine BBIBP-CorV, whereas the CD4+ T-cell mediated cellular activity was highest in HDs vaccinated with BBIBP-CorV. LA - English DB - MTMT ER - TY - JOUR AU - Aringer, Martin AU - Costenbader, Karen AU - Daikh, David AU - Brinks, Ralph AU - Mosca, Marta AU - Ramsey-Goldman, Rosalind AU - Smolen, Josef S AU - Wofsy, David AU - Boumpas, Dimitrios T AU - Kamen, Diane L AU - Jayne, David AU - Cervera, Ricard AU - Costedoat-Chalumeau, Nathalie AU - Diamond, Betty AU - Gladman, Dafna D AU - Hahn, Bevra AU - Hiepe, Falk AU - Jacobsen, Søren AU - Khanna, Dinesh AU - Lerstrøm, Kirsten AU - Massarotti, Elena AU - McCune, Joseph AU - Ruiz-Irastorza, Guillermo AU - Sanchez-Guerrero, Jorge AU - Schneider, Matthias AU - Urowitz, Murray AU - Bertsias, George AU - Hoyer, Bimba F AU - Leuchten, Nicolai AU - Tani, Chiara AU - Tedeschi, Sara K AU - Touma, Zahi AU - Schmajuk, Gabriela AU - Anic, Branimir AU - Assan, Florence AU - Chan, Tak Mao AU - Clarke, Ann Elaine AU - Crow, Mary K AU - Czirják, László AU - Doria, Andrea AU - Graninger, Winfried AU - Halda-Kiss, Bernadett AU - Hasni, Sarfaraz AU - Izmirly, Peter M AU - Jung, Michelle AU - Kumánovics, Gábor AU - Mariette, Xavier AU - Padjen, Ivan AU - Pego-Reigosa, José M AU - Romero-Diaz, Juanita AU - Rúa-Figueroa Fernández, Íñigo AU - Seror, Raphaèle AU - Stummvoll, Georg H AU - Tanaka, Yoshiya AU - Tektonidou, Maria G AU - Vasconcelos, Carlos AU - Vital, Edward M AU - Wallace, Daniel J AU - Yavuz, Sule AU - Meroni, Pier Luigi AU - Fritzler, Marvin J AU - Naden, Ray AU - Dörner, Thomas AU - Johnson, Sindhu R TI - 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus JF - ARTHRITIS & RHEUMATOLOGY J2 - ARTHRITIS RHEUMATOL VL - 71 PY - 2019 IS - 9 SP - 1400 EP - 1412 PG - 13 SN - 2326-5191 DO - 10.1002/art.40930 UR - https://m2.mtmt.hu/api/publication/30759962 ID - 30759962 N1 - This article is published simultaneously in the September 2019 issue of Annals of the Rheumatic Diseases AB - To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects.The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Enikő AU - Hornung, Ákos AU - Monostori, Éva AU - Bocskai, Márta AU - Czibula, Ágnes AU - Kovács, László TI - Altered Cell Surface N-Glycosylation of Resting and Activated T Cells in Systemic Lupus Erythematosus JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 20 PY - 2019 IS - 18 PG - 14 SN - 1661-6596 DO - 10.3390/ijms20184455 UR - https://m2.mtmt.hu/api/publication/30802849 ID - 30802849 N1 - Institute of Genetics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, 6726, Hungary Department of Rheumatology and Immunology, Faculty of Medicine, University of Szeged, Szeged, 6725, Hungary Export Date: 29 November 2019 Correspondence Address: Czibula, Á.; Institute of Genetics, Biological Research Centre of the Hungarian Academy of SciencesHungary; email: czibula.agnes@brc.hu Chemicals/CAS: galectin 1, 258495-34-0; sialidase, 9001-67-6; sialyltransferase, 9075-81-4 Institute of Genetics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, 6726, Hungary Department of Rheumatology and Immunology, Faculty of Medicine, University of Szeged, Szeged, 6725, Hungary Export Date: 2 December 2019 Correspondence Address: Czibula, Á.; Institute of Genetics, Biological Research Centre of the Hungarian Academy of SciencesHungary; email: czibula.agnes@brc.hu Chemicals/CAS: galectin 1, 258495-34-0; sialidase, 9001-67-6; sialyltransferase, 9075-81-4 AB - Altered cell surface glycosylation in congenital and acquired diseases has been shown to affect cell differentiation and cellular responses to external signals. Hence, it may have an important role in immune regulation; however, T cell surface glycosylation has not been studied in systemic lupus erythematosus (SLE), a prototype of autoimmune diseases. Analysis of the glycosylation of T cells from patients suffering from SLE was performed by lectin-binding assay, flow cytometry, and quantitative real-time PCR. The results showed that resting SLE T cells presented an activated-like phenotype in terms of their glycosylation pattern. Additionally, activated SLE T cells bound significantly less galectin-1 (Gal-1), an important immunoregulatory lectin, while other lectins bound similarly to the controls. Differential lectin binding, specifically Gal-1, to SLE T cells was explained by the increased gene expression ratio of sialyltransferases and neuraminidase 1 (NEU1), particularly by elevated ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 (ST6GAL1)/NEU1 and ST3 beta-galactoside alpha-2,3-sialyltransferase 6 (ST3GAL6)/NEU1 ratios. These findings indicated an increased terminal sialylation. Indeed, neuraminidase treatment of cells resulted in the increase of Gal-1 binding. Altered T cell surface glycosylation may predispose the cells to resistance to the immunoregulatory effects of Gal-1, and may thus contribute to the pathomechanism of SLE. LA - English DB - MTMT ER - TY - JOUR AU - Deák, Magdolna AU - Hornung, Ákos AU - Novák, Julianna AU - Demydenko, Dmytro AU - Szabó, Enikő AU - Czibula, Ágnes AU - Fajka-Boja, Roberta AU - Kriston-Pál, Éva AU - Monostori, Éva AU - Kovács, László TI - Novel role for galectin-1 in T-cells under physiological and pathological conditions JF - IMMUNOBIOLOGY J2 - IMMUNOBIOLOGY VL - 220 PY - 2015 IS - 4 SP - 483 EP - 489 PG - 7 SN - 0171-2985 DO - 10.1016/j.imbio.2014.10.023 UR - https://m2.mtmt.hu/api/publication/2807186 ID - 2807186 N1 - Cited By :19 Export Date: 13 July 2022 CODEN: ZIMMD AB - Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1) has been described as a strong immunosuppressive protein due to its major activity of inducing apoptosis of activated T-cells. It has previously been reported that T-cells express Gal-1 upon activation, however its participation in T-cell functions has remained largely elusive. To determine function of Gal-1 expressed by activated T-cells we have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1. Rather, a particular consequence of the inGal-1 expression was that T-cells became more sensitive to exGal-1 added either as a soluble protein or bound to the surface of a Gal-1-secreting effector cell. This was also verified when the susceptibility of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with activated T-cells from patients with systemic lupus erythematosus (SLE), a disease in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency in lupus. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Ferenc AU - Blaskó, Andrea AU - Fajka-Boja, Roberta AU - Katona, Róbert László AU - Végh, Lea AU - Novák, Julianna AU - Szebeni, Gábor AU - Krenács, László AU - Uher, Ferenc AU - Tubak, Vilmos AU - Kiss, R AU - Monostori, Éva TI - Mechanism of tumor cell-induced T-cell apoptosis mediated by galectin-1 JF - IMMUNOLOGY LETTERS J2 - IMMUNOL LETT VL - 127 PY - 2010 IS - 2 SP - 108 EP - 118 PG - 11 SN - 0165-2478 DO - 10.1016/j.imlet.2009.10.003 UR - https://m2.mtmt.hu/api/publication/1303865 ID - 1303865 N1 - Megjegyzés-22175938 DI: 10.1016/j.imlet.2009.10.003 Megjegyzés-22193511 DI: 10.1016/j.imlet.2009.10.003 Megjegyzés-20893666 UR: http://www.scopus.com/inward/record.url?eid=2-s2.0-71649092570&partnerID=40&md5=5bd1ae42d9e527aefe59878f02f5d515 Megjegyzés-21955783 Chemicals/CAS: caspase, 186322-81-6; galectin 1, 258495-34-0; protein kinase Lck, 114051-78-4; protein kinase ZAP 70, 148047-34-1; Caspases, 3.4.22.-; Galectin 1; Lymphocyte Specific Protein Tyrosine Kinase p56(lck), 2.7.10.2; Neoplasm Proteins; RNA, Small Interfering; ZAP-70 Protein-Tyrosine Kinase, 2.7.10.2 Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Temesvári krt. 62, H-6726 Szeged, Hungary Laboratory of Tumor Pathology and Molecular Diagnostics, Hungary Stem Cell Biology, National Blood Service, Hungary Institute of Biochemistry, Biological Research Center, Hungarian Academy of Sciences, Hungary Laboratory of Toxicology, Institute of Pharmacy, Université Libre de Bruxelles (ULB), Brussels, Belgium Cited By :53 Export Date: 10 February 2021 CODEN: IMLED Correspondence Address: Monostori, E.; Institute of Genetics, Temesvári krt. 62, H-6726 Szeged, Hungary; email: monos@brc.hu AB - Galectin-1 (Gal-1) has been implicated in tumor progression partly via the induction of T-cell apoptosis. However the mechanism of Gal-1 induced T-cell death was mostly studied using recombinant, soluble Gal-1 producing controversial results. To explore the true mechanism of Gal-1 and hence tumor cell-induced T-cell death, we applied co-cultures of tumor cells and T-cells thus avoiding artificial circumstances generated using recombinant protein. T-cells died when co-cultured with Gal-1-expressing but survived with Gal-1 non-expressing tumor cells. Removing tumor cell surface Gal-1 or knocking down Gal-1 expression resulted in diminution of T-cell apoptosis. Gal-1 transgenic or soluble Gal-1 treated HeLa cells became cytotoxic. Stimulation of apoptosis required interaction between the tumor and T-cells, presence of p56lck and ZAP70, decrease of mitochondrial membrane potential and caspase activation. Hence tumor cell-derived Gal-1 might efficiently contribute to tumor self-defense. Moreover this system resolves the discrepancies obtained using recombinant Gal-1 in T-cell apoptosis studies. © 2009 Elsevier B.V. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Fajka-Boja, Roberta AU - Blaskó, Andrea AU - Kovács-Sólyom, F AU - Szebeni, Gábor AU - Tóth, Gábor AU - Monostori, Éva TI - Co-localization of galectin-1 with GM1 ganglioside in the course of its clathrin- and raft-dependent endocytosis JF - CELLULAR AND MOLECULAR LIFE SCIENCES J2 - CELL MOL LIFE SCI VL - 65 PY - 2008 IS - 16 SP - 2586 EP - 2593 PG - 8 SN - 1420-682X DO - 10.1007/s00018-008-8143-x UR - https://m2.mtmt.hu/api/publication/1303868 ID - 1303868 N1 - Megjegyzés-22175944 DI: 10.1007/s00018-008-8143-x Megjegyzés-22193519 DI: 10.1007/s00018-008-8143-x Megjegyzés-21955794 Chemicals/CAS: galectin 1, 258495-34-0; ganglioside GM1, 37758-47-7; leukosialin, 123897-54-1; Antigens, CD7; Clathrin; G(M1) Ganglioside, 37758-47-7; Galectin 1; Ligands AB - Mammalian galectin-1 (Gal-1), a β-galactoside-binding lectin has a prominent role in regulating cell adhesion, cell growth and immune responses. Downregulation of these biological functions may occur via internalization of Gal-1. In the present study we have investigated the mechanism and possible mediator(s) of Gal- 1 endocytosis. We show that internalization occurs at a temperature higher than 22°C in an energy dependent fashion. After one hour incubation Gal-1 localizes in the Golgi system within the cells, and then disappears without accumulation in degradation compartments, such as lysosomes. Based on their strong intracellular co-localization, two glycoconjugates, GM1 ganglioside and CD7 are implicated in the sorting of internalized Gal-1 into Golgi. Other known Gal-1 binding glycoproteins on T cells (CD2, CD3, CD43 and CD45) do not cointernalize with the lectin. Internalization of Gal-1 depends on its lectin activity and follows dual pathways involving clathrin-coated vesicles and raft-dependent endocytosis. © 2008 Birkhaueser. LA - English DB - MTMT ER - TY - JOUR AU - Fajka-Boja, Roberta AU - SZEMES, M AU - Ion, Gabriella AU - Légrádi, Ádám AU - CARON, M AU - Monostori, Éva TI - Receptor tyrosine phosphatase, CD45 binds galectin-1 but does not mediate its apoptotic signal in T cell lines JF - IMMUNOLOGY LETTERS J2 - IMMUNOL LETT VL - 82 PY - 2002 SP - 149 EP - 154 PG - 6 SN - 0165-2478 DO - 10.1016/S0165-2478(02)00030-5 UR - https://m2.mtmt.hu/api/publication/1912392 ID - 1912392 N1 - WoS:hiba:000176059200020 2019-03-03 14:34 cikkazonosító nem egyezik Lymphocyte Signal Transduction Laboratory, Institute of Genetics, Hungarian Academy of Sciences, P.O. Box 521, Temesvari krt. 62, H-6726 Szeged, Hungary Equipe De Biochimie Des Portéines Et Protéomique, Group De Recherche En Immunopathologie Et Immuno Intervention, Université Paris 13, 93017 Bobigny, France Cited By :33 Export Date: 9 May 2021 CODEN: IMLED Correspondence Address: Monostori, É.; Lymphocyte Signal Transduction Lab., Temesvári krt. 62, H-6726 Szeged, Hungary; email: monos@nucleus.szbk.u-szeged.hu LA - English DB - MTMT ER -