Ludwik Hirszfeld Institute of Immunology and Experimental Therapy

Wrocław, Poland

Ludwik Hirszfeld Institute of Immunology and Experimental Therapy

Wrocław, Poland

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Cebula A.,Georgia Regents University | Seweryn M.,Ohio State University | Seweryn M.,University of Lodz | Rempala G.A.,Ohio State University | And 7 more authors.
Nature | Year: 2013

Peripheral mechanisms preventing autoimmunity and maintaining tolerance to commensal microbiota involve CD4 + Foxp3 + regulatory T (T reg) cells generated in the thymus or extrathymically by induction of naive CD4 + Foxp3-T cells. Previous studies suggested that the T-cell receptor repertoires of thymic T reg cells and induced T reg cells are biased towards self and non-self antigens, respectively, but their relative contribution in controlling immunopathology, such as colitis and other untoward inflammatory responses triggered by different types of antigens, remains unresolved. The intestine, and especially the colon, is a particularly suitable organ to study this question, given the variety of self-, microbiota-and food-derived antigens to which T reg cells and other T-cell populations are exposed. Intestinal environments can enhance conversion to a regulatory lineage and favour tolerogenic presentation of antigens to naive CD4 + T cells, suggesting that intestinal homeostasis depends on microbiota-specific induced T reg cells. Here, to identify the origin and antigen-specificity of intestinal T reg cells, we performed single-cell and high-throughput sequencing of the T-cell receptor repertoires of CD4 + Foxp3 + and CD4 + Foxp3-T cells, and analysed their reactivity against specific commensal species. We show that thymus-derived T reg cells constitute most T reg cells in all lymphoid and intestinal organs, including the colon, where their repertoire is heavily influenced by the composition of the microbiota. Our results suggest that thymic T reg cells, and not induced T reg cells, dominantly mediate tolerance to antigens produced by intestinal commensals. © 2013 Macmillan Publishers Limited. All rights reserved.

Nowak B.,Jagiellonian University | Ciszek-Lenda M.,Jagiellonian University | Srottek M.,Jagiellonian University | Gamian A.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | And 3 more authors.
Archivum Immunologiae et Therapiae Experimentalis | Year: 2012

Oral administration of some probiotic bacteria (e.g. Lactobacillus rhamnosus) attenuates various types of experimental arthritis, including collagen-induced arthritis (CIA) and inhibits arthritogenic autoantibodies. Much less is known about the possible anti-arthritogenic properties of exopolysaccharide (EPS), the major component of lactic bacteria biofilm. In this study, we asked the question whether systemic administration of EPS derived from L. rhamnosus KL37 depresses the production of anti-collagen IgG and affects the development of CIA in DBA/1 mice. Arthritis was induced employing two models of active CIA, in which mice were immunized with type II collagen (CII) either in the presence of lipopolysaccharide (LPS; mild arthritis with moderate CII-specific IgG production) or with Complete Freund's Adjuvant and LPS (severe arthritis with massive CII-specific IgG production). Passive CIA was induced by intravenous injection of CII-specific monoclonal antibodies and LPS. Disease progression, the incidence and severity of arthritis, were determined. Serum concentration of CII-specific IgG was measured by enzyme-linked immunosorbent assay. Systemic administration of EPS markedly reduced CII-specific antibody production. Moreover, EPS significantly ameliorated arthritis in the active models of CIA, especially, when LPS alone was used as an adjuvant. In contrast, when arthritogenic antibodies were injected to mice in high amounts, the effect of EPS on the development of passive CIA was negligible and transient. These results show that EPS can suppress active CIA by the inhibition of arthritogenic antibodies production. Therefore, we suggest that EPS or EPS-producing probiotics may be promising agents for the supporting therapy of patients with rheumatoid arthritis. © L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2012.

Hojka-Osinska A.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | Ziolo E.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | Rapak A.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
Biochemical and Biophysical Research Communications | Year: 2012

Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergistic effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug-indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death. © 2012 Elsevier Inc..

Pawlak A.,Wrocław University of Environmental and Life Sciences | Rapak A.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | Zbyryt I.,Wrocław University of Environmental and Life Sciences | Obminska-Mrukowicz B.,Wrocław University of Environmental and Life Sciences
In Vivo | Year: 2014

Background/Aim: Lymphoma, the most common hematopoietic cancer in dogs is sensitive to chemotherapy which is the dominant treatment method. The aim of the present study was to evaluate the concentration-dependent cytotoxicity and ability to induce apoptosis of the antineoplastic agents cyclophosphamide (CYC), chlorambucil (CBL), cytosine arabinoside (ARA), dexamethasone (DEX), doxorubicin (DOX), etoposide (ETO), lomustine (LOM), prednisone (PRED) and vincristine (VINK) against GL-1, CL-1, CLBL-1 and Jurkat cell lines. Materials and Methods: To determine cell viability and level of apoptosis, three different tests were performed: Thiazolyl Blue Tetrazolium Bromide (MTT), annexin V/propidium iodide (An/PI) staining and flow cytometric DNA fragmentation. Results: All tested substances exhibited concentration-dependent inhibitory effects on the proliferation of the examined cell lines with a different level of apoptosis induction. VINK and DOX strongly decreased the viability of canine cell lines, whereas CYC induced the highest level of apoptosis. Conclusion: Canine lymphoma (CL-1, CLBL-1) and leukemia (GL-1) cell lines are a useful tool for developing new and more effective treatment regimes for canine neoplasia.

Paprocka M.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | Paprocka M.,CNRS Center for Molecular Biophysics | Krawczenko A.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | Dus D.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | And 4 more authors.
Cytometry Part A | Year: 2011

Endothelial progenitor cells (EPCs) modulate postnatal vascularization and contribute to vessel regeneration in adults. Stem cells and progenitor cells were found in umbilical cord blood, bone marrow, and mobilized peripheral blood cells, from where they were isolated and cultured. However, the yield of progenitor cells is usually not sufficient for clinical application and the quality of progenitor cells varies. The aim of the study was the immortalization of early progenitor cells with high proliferative potential, capable to differentiate to EPCs and, further, toward endothelial cells. Two cell lines, namely HEPC-CB.1 and HEPC-CB.2 (human endothelial progenitor cells-cord blood) were isolated. As assessed by specific antibody labeling and flow cytometric analysis, they express a panel of stem cell markers: CD133, CD13, CD271, CD90 and also endothelial cell markers: CD202b, CD309 (VEGFR2), CD146, CD105, and CD143 but they do not present markers of finally differentiated endothelial cells: CD31, vWf, nor CD45 which is a specific hematopoietic cell marker. Using the multiplex Cytometric Bead Assay, the simultaneous production of proangiogenic cytokines IL8, angiogenin, and VEGF was demonstrated in normoxia and was shown to be increased by hypoxia. Both cell lines, similarly as mature endothelial cells, underwent in vitro pre-angiogenic process, formed pseudovessel structures and present an accelerated angiogenesis in hypoxic conditions. To date, these are the first CD133 positive established cell lines from human cord blood cells. © 2011 International Society for Advancement of Cytometry © 2011 International Society for Advancement of Cytometry.

Masternak J.,Jan Kochanowski University | Barszcz B.,Jan Kochanowski University | Sawka-Dobrowolska W.,Wrocław University | Wietrzyk J.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | And 2 more authors.
RSC Advances | Year: 2014

We have demonstrated a simple process that involves one-pot, one-step reactions leading to efficient preparation of new cadmium complexes with N4-donating ligands [CdX2L1] (X = I- (1), Br- (2) L1 = tris(1-(3,5-dimethylpyrazolyl)methyl)amine). The most prominent feature of the synthesis is the in situ formation of a new organic tripodal ligand (L1) in a condensation reaction between a starting ligand (1-hydroxymethyl-3,5-dimethylpyrazole) and ammonia. A single-crystal X-ray analysis confirmed that the complexes obtained are monomers (1, 2) with octahedral geometry of the cadmium centres. Complex 3 has a cationic-anionic structure [Cu(LOH)2CH3OH][CdCl4] and has been synthesised by the reaction of CdO and NH4Cl in the presence of zerovalent copper (powder). IR, EPR, 1H and 13C NMR, as well as simultaneous TG/DTG were carried out to characterise the products. Moreover, we try to compare the cytotoxic profile of CdO and cadmium salts with Cd(ii) complexes. Besides [CdX2L1] (1, 2) we take into consideration [Cd2(L2)2(SCN)4(MeOH)2]n (4) and [Cd(SCN)2L1] (5) complexes. Biological studies demonstrated that Cd(ii) complexes with the N-scorpionate ligand (1, 2 and 5) have similar cytotoxicity, which points to a structure-cytotoxicity relationship. Thus, all the complexes (except 4) exhibited a lower cytotoxic activity compared to a cadmium ion in salts. This journal is © the Partner Organisations 2014.

PubMed | Wrocław University of Environmental and Life Sciences and Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
Type: | Journal: Veterinary and comparative oncology | Year: 2016

Lymphoma is the most frequently diagnosed cancer of the canine haematopoietic system. In this study, the flow cytometry and polymerase chain reaction (PCR) analysis were used to characterize a series of canine lymphomas in detail. The aim of this study was to determine the incidence of B- and T-cell high-grade lymphomas and their immunophenotypic characterization in Lower Silesia, Poland. The results show that the frequency of each type of lymphoma is 71% for B-cell and 17% for T-cell lymphomas. In two cases the PCR techniques confirmed the presence of simultaneous double gene rearrangements of the BCR and TCR receptors.

PubMed | Wrocław University of Environmental and Life Sciences and Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
Type: | Journal: Chemico-biological interactions | Year: 2016

Four stereoisomers of -iodo--lactones with p-isopropylphenyl substituent at -position: cis-(4R,5R,6S)-1, cis-(4S,5S,6R)-2, trans-(4R,5S,6R)-3, trans-(4S,5R,6S)-4 with proved antiproliferative activity were subjected to invitro tests for a better understanding of their anticancer activity. The subject of our interest was a possible relationship between a configuration of chiral centers of the studied lactones and their anticancer potency against a panel of canine cell lines representing hematopoietic (CLBL-1, GL-1, CL-1, CLB70) and mammary gland cancers (P114, CMT-U27, CMT-U309). To determine the anticancer activity of the tested compounds, cell viability and cell metabolic activity were checked using propidium iodide staining and the MTT test. To determine whether the studied compounds cause necrotic or apoptotic cell death, two assays for apoptosis evaluation were performed, annexin V staining and detection of caspase 3/7 activation. Simultaneously, the effects of the compounds on the cell cycle were also examined. The conducted research confirmed the anticancer potential of the tested lactones against canine cancers. The investigated isomers exerted higher activity against canine lymphoma/leukemia cell lines than against mammary tumors, whereas the configuration of stereogenic centers of the examined compounds affected their activity. It has been shown that stereoisomers with 4S configuration (2,4) were more active, and the most potent one was the cis-(4S,5S,6R)-2 isomer. The investigated lactones seemed to initiate the process of apoptosis rather than acting as typical cytostatic agents, as cell death via apoptosis, and no increase in G2-M population in the cell cycle analysis were observed. The presented study demonstrated that all four stereoisomers of -iodo--lactones with p-isopropylphenyl substituent at -position induced apoptosis via a mitochondrial-mediated, caspase-dependent pathway.

PubMed | Wrocław University of Environmental and Life Sciences, Wroclaw Medical University and Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
Type: | Journal: Veterinary and comparative oncology | Year: 2016

We established a new B-cell leukaemia cell line CLB70 from a dog with chronic lymphocytic leukaemia. This cell line is positive for CD20, CD45, CD79a, MHC class II, IgG, IgM; weakly positive for CD21; and negative for CD3, CD4, CD5, CD8, CD14, CD34, CD117. PCR for antigen receptor gene rearrangement (PARR) analysis revealed a biclonal immunoglobulin heavy chain (IgH) gene rearrangement and negative result for TCR. Western blot analysis of anti- and pro-apoptotic proteins showed increased expression of Bcl-2, Mcl-1, NF-kB, and Ras, and decreased expression of p53. CLB70 cells grow rapidly in vitro and are tumourigenic in nude mice. The CLB70 line is highly sensitive to doxorubicin, less sensitive to etoposide and imatinib, and resistant to piroxicam, celecoxib and dexamethasone. Our results indicate that CLB70 cells are derived from mature B-cells and they may be a useful tool for the development of new therapeutic strategies for both dogs and humans.

Kaczmarek R.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | Buczkowska A.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | Buczkowska A.,Polish Academy of Sciences | Mikolajewicz K.,Ludwik Hirszfeld Institute of Immunology and Experimental Therapy | And 3 more authors.
Transfusion Medicine Reviews | Year: 2014

Antigens belonging to the P1PK, GLOB, and FORS blood group systems and the GLOB blood group collection represent a closely related set of 13 glycosphingolipids (GSLs). They are synthesized by the coordinated action of glycosyltransferases, encoded by at least 7 different loci. Three of these enzymes show either different activity or a different mRNA expression profile due to genetic polymorphisms, resulting in blood group diversity. In recent years, significant progress has been made in understanding the molecular background and biological functions of these GSLs. Their medical significance is often related to the existence of natural antibodies, as they may cause complications after transfusions and during pregnancies. In addition, GSLs belonging to these blood group systems are receptors for several pathogens. This review summarizes the present knowledge about the complicated network of enzymatic interactions leading to synthesis of these GSLs, as well as their clinical implications. © 2014 Elsevier Inc.

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