Aleksandra Szteblich
Polish Academy of Sciences
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Featured researches published by Aleksandra Szteblich.
Pathology & Oncology Research | 2012
Agata Kosmaczewska; Dorota Bocko; Lidia Ciszak; Iwona Wlodarska-Polinska; Jan Kornafel; Aleksandra Szteblich; Anna Masternak; Irena Frydecka
Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients’ T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression.
Postȩpy higieny i medycyny doświadczalnej | 2014
Magdalena Szmyrka-Kaczmarek; Agata Kosmaczewska; Lidia Ciszak; Aleksandra Szteblich; Piotr Wiland
INTRODUCTION The balance between proinflammatory Th17 cells and regulatory T cells plays an important role in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). In particular, an increased ratio of Th17/Treg cells has been shown to correlate with active SLE and specific organ involvement. The aim of our study was to assess Th17 and Treg cell populations in peripheral blood (PB) of patients with clinically quiescent SLE, and to evaluate their correlation with organ involvement. MATERIAL/METHODS We performed flow cytometric analysis of studied T CD4+ cell subpopulations in PB from 21 patients with SLE and 13 healthy controls. Disease activity was measured with the SELENA-SLEDAI index; organ involvement was divided into renal, neurological and hematological. RESULTS A statistically significant difference (p<0.01) between the mean percentages of CD4+CD25highFoxP3+ Treg cells in SLE patients (18.57%) and healthy controls (32.08%) was observed. Similarly, proportions of functional CTLA-4+ Treg cells were markedly lower in SLE patients than in healthy controls--19.3% vs. 23.82% (p=0.03). In contrast, SLE patients exhibited a significantly increased frequency of circulating Th17 cells with the phenotype CD4+IL-17+ compared to controls--1.36 % vs 0.19% (p<0.01). Also the ratio of Th17 cells to Th1 cells was markedly higher in SLE patients than in the control group (p<0.01). We did not find any correlation of PB Th cell distribution with organ involvement in SLE patients examined. CONCLUSIONS Our report showed for the first time that systemic Th17/Treg imbalance occurred also in patients with low disease activity and in remission. We suggest that immunological alterations may precede clinical and laboratory symptoms of the disease activity.
Inflammation | 2015
Agata Kosmaczewska; Lidia Ciszak; Jerzy Swierkot; Aleksandra Szteblich; Katarzyna Kosciow; Irena Frydecka
Interleukin-2 (IL-2) has been suggested to control Treg/Th17 balance. Recently, we reported a relationship of rheumatoid arthritis (RA) activity/progression with irreversible systemic Treg and Th1 defects including serum IL-2 shortage. Herein, we explore the role of in vitro stimulation with rIL-2 in the observed immune alterations reversal. Patients with stable or progressive RA were assigned to methotrexate (MTX) group or to TNF-alpha inhibitors (iTNF) group, respectively. Flow cytometric analyses were performed before and after 6 months of treatment. Circulating Th1, Th17, and Treg cells were determined before and after 72-h culture with anti-CD3 + rIL-2. Before therapy, 72-h stimulation restored recently observed phenotypic Th cell alterations, except for the enriched Th17 subset normalized as late as after therapy in all patients. Under 6-month therapy, anti-CD3 stimulation changed the Th cell distribution only in progressive RA; despite Th1 enrichment, it revealed Treg population defects, which were completely reversed by exogenous IL-2 added to the stimulating culture. Our paper shows that in aggressive RA patients exhibiting serum IL-2 shortage despite iTNF therapy, exogenous rIL-2 is capable of promoting Treg differentiation affected by chronic activation, thus supporting its use in the combined strategy of biologic treatment of the progressive form of RA.
Pediatric Nephrology | 2010
Kinga Musiał; Lidia Ciszak; Agata Kosmaczewska; Aleksandra Szteblich; Irena Frydecka; Danuta Zwolińska
The idiopathic nephrotic syndrome (INS) has been related to cellular immune disturbances. The zeta (ζ) chain, a component of the T-cell receptor/CD3 (TCR) complex and CD16 heterodimer in NK cells, plays a crucial role in T and NK cell activation and proliferation. The aim of our study was to examine zeta chain expression in CD4+, CD8+ T lymphocytes and NK cells in the peripheral blood of children with INS and to evaluate the effect of anti-CD3+rIL-2 stimulation on the level of zeta chain expression in the INS pediatric population. The study group consisted of 15 children with INS in relapse, 16 patients with INS in clinical remission, and 17 controls. The percentage of zeta-positive cells and the values of mean fluorescence intensity (MFI) were determined by flow cytometry. Compared with that in the controls, the percentage of zeta+ freshly isolated NK cells in children with INS in relapse was significantly lower, whereas, in CD3+/CD4+ and CD3+/CD8+ populations, no alteration was observed. There were no differences in the MFI values between the populations of freshly isolated cells either. Stimulation with anti-CD3+rIL-2 decreased the percentage of zeta+/CD4+ T cells and NKzeta+ cells in a significant way in all the groups analysed, whereas the percentage of zeta+/CD8+ T cells decreased significantly only in patients with INS in relapse. The altered pattern of zeta expression in fresh NK cells from children with INS in relapse, and the disturbed response of zeta+/CD8+ T cells to anti-CD3+rIL-2 stimulation in relapse, suggests the possible role of this chain in immune dysregulation in INS, particularly with regard to cytotoxic cells.
Tumor Biology | 2016
Lidia Ciszak; Irena Frydecka; Dariusz Wolowiec; Aleksandra Szteblich; Agata Kosmaczewska
Recently, systemic administration of a human monoclonal antibody directed against cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expressed on circulating T cells in patients with chronic lymphocytic leukaemia (CLL) has been considered. Also, CLL cells have been shown to express CTLA-4, increased levels of which in the leukaemic compartment are a predictor of good clinical outcome. Since both CLL and Treg microenvironment cells can be targeted by the CTLA-4 blocking antibody in this immunotherapy approach, the investigation of the functional effect of CTLA-4 blockade on CLL cells might be of potential clinical relevance. The main aim of this study was to examine the effect of CTLA-4 blockade on proliferation activity and apoptosis of CLL cells in patients with low and high CTLA-4 expression. We found that in the high CTLA-4-expressing CLL group, CTLA-4 blockade on the CLL cell surface resulted in a significant increase in the median percentages of Ki67+ cells and a tendency to decrease in the proportion of apoptotic cells. In contrast, in the low CTLA-4 expressors, CTLA-4 blockade did not affect the proliferation activity or the frequency of apoptosis. This study reports for the first time the different effect of CTLA-4 blockade on CLL cells in CLL patients depending on the levels of CTLA-4 expression. CTLA-4 blockade seems to induce pro-survival signals in leukaemic cells from CLL patients exhibiting high CTLA-4 expression, suggesting that an immunotherapy approach based on the systemic use of monoclonal anti-CTLA-4 antibodies could be an unfavourable strategy for some CLL patients.
Pathology & Oncology Research | 2014
Agata Kosmaczewska; Lidia Ciszak; Jerzy Swierkot; Aleksandra Szteblich; Piotr Wiland; Irena Frydecka
The chronic nature of rheumatoid arthritis (RA) suggests immune dysfunction, including persistent systemic activation. Therefore, we evaluated the activatory and inhibitory potential as well as proliferative activity of peripheral blood (PB) CD4+ T cells from RA patients in different stages of the disease and after different therapeutic interventions. We found that CD4+ T cells from RA patients were activated in vivo concerning decreased CD28 expression and increase of CD40L, CD69, and CTLA-4 expression; however, the extent of stimulation was suboptimal when compared to healthy controls. Consequently, impaired proliferative activities of these cells were found in all patients irrespective of the active disease duration. Treatment with methotrexate (MTX) and/or inhibitors of TNF-alpha (iTNF) did not significantly influence systemic activation in RA patients, which corresponded with the maintenance of inflammation markers; however, partial restoration of CD28 and CTLA-4 expression as well as clinical improvement were observed. In patients with early disease (the MTX group), we noted higher capacity of CD4+ T cells for restoration of T cell function, whereas cells from the iTNF group with progressive disease remained with a proliferative defect after the treatment. In conclusion, our study demonstrates that the dysregulated expression of molecules interfering with CD4+ T cell signaling may result in functional impairment of the effector T cells and correlates with disease progression.
Clinical and Experimental Medicine | 2016
Lidia Ciszak; Irena Frydecka; Dariusz Wolowiec; Aleksandra Szteblich; Agata Kosmaczewska
Previously, we showed that cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is overexpressed in chronic lymphocytic leukaemia (CLL) and its expression is correlated with the expression of the major regulators of G1 phase progression: cyclins D2 and D3, and cyclin-dependent kinase inhibitory protein 1 (p27KIP1). In the present study, we blocked CTLA-4 on the surface of both CLL cells and normal B lymphocytes to investigate the impact of CTLA-4 on the expression of the mentioned G1 phase regulators. We found that in CLL patients and in healthy individuals, the median proportions of cyclin D2-positive cells as well as cyclin D3+ cells significantly decreased following CTLA-4 blockade. Moreover, CTLA-4 blockade led to an increase in the median frequencies of p27KIP1-positive cells, although this increase was marked only in CLL patients. Our study showed that CTLA-4 affects the expression of the key regulators of G1 phase progression in CLL cells as well as in normal B lymphocytes and may contribute to a better understanding of the role of CTLA-4 in the regulation of G1 phase progression.
Oncology Research | 2009
Agata Kosmaczewska; Lidia Ciszak; Aleksandra Szteblich; Anna Laba; Marcin Wojtowicz; Dariusz Wolowiec; Irena Frydecka
The most recent studies emphasize a link between B-cell proliferation in vivo and clinical outcome of B-cell chronic lymphocytic leukemia (B-CLL). The expression of cyclin D2 in B-CLL cells isolated from the peripheral blood of 27 untreated patients in relation to the apoptosis ratio both before and 72 h after culture in the absence of growth factors was analyzed by immunocytochemistry. The significant associations between cell death in culture and both cyclin D2 expression in freshly isolated cells and the rate of its decrement in culture found in this study confirm the special role of cyclin D2 in enhancing the longevity of these cells in vivo. As cyclin D2 is inducible in the early G1 phase, its increased expression might also reflect the activation of cells attempting to replicate in vivo. Furthermore, the finding that B-CLL progression positively correlates with the gradual increase in the proportion of apoptotic B lymphocytes in culture seems to support the notion of cells striving to undergo division in the absence of growth factors. All together, these results indicate the possibility that cyclin D2+ cells represent a pool of leukemic cells with the potential to enter the dividing compartment.
Transplant Immunology | 2006
Agata Kosmaczewska; M. Magott-Procelewska; Irena Frydecka; Lidia Ciszak; Dorota Bocko; Aleksandra Szteblich; Piotr Kusnierczyk; D. Patrzałek; Piotr Szyber; Marian Klinger
Oncology Reports | 1994
Lidia Ciszak; Agata Kosmaczewska; Bozena Werynska; Aleksandra Szteblich; Renata Jankowska; Irena Frydecka