Lidia Ciszak
Research interests
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InterestsFlow Cytometry, Cell Culture
Publications
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1.30Impact points
Stimulated peripheral production of interferon-gamma is related to fatigue and depression in multiple sclerosis.
Clinical neurology and neurosurgery. 03/2012;
OBJECTIVES: The aim of the study was to evaluate the stimulated production of interferon-gamma (IFNγ) by peripheral CD3+CD4+ T lymphocytes in patients with multiple sclerosis (MS) with regard to the degree of fatigue, and to investigate relationships between immunological parameters, level of depres... [more] OBJECTIVES: The aim of the study was to evaluate the stimulated production of interferon-gamma (IFNγ) by peripheral CD3+CD4+ T lymphocytes in patients with multiple sclerosis (MS) with regard to the degree of fatigue, and to investigate relationships between immunological parameters, level of depression and clinical variables. METHODS: Forty MS patients (30 women, 10 men, aged 22-60 years): 20 fatigued and 20 non-fatigued were involved in the study. Fatigue was evaluated using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS), depression level - using Beck Depression Inventory (BDI). Production of IFNγ by stimulated peripheral blood CD3+CD4+ T lymphocytes, assessed using flow cytometry, was compared between MS patients with different levels of fatigue and controls. Correlations were searched out between immunological findings and BDI, age, duration and course of MS, relapse rate, disability (assessed in Expanded Disability Status Scale - EDSS) and its progression. RESULTS: Stimulated production of IFNγ by CD3+CD4+ T lymphocytes was higher in severely fatigued patients in comparison with non-fatigued ones and controls, tended to correlate with FSS and MFIS, and correlated with BDI. No relationships were found between immunological findings and disease-related variables. CONCLUSION: Stimulated production of IFNγ by peripheral CD3+CD4+ T lymphocytes is related to fatigue and depression in MS patients.
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1.15Impact points
Dysregulated Expression of Both the Costimulatory CD28 and Inhibitory CTLA-4 Molecules in PB T Cells of Advanced Cervical Cancer Patients Suggests Systemic Immunosuppression Related to Disease Progression.
Pathology oncology research : POR. 11/2011;
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 ... [more] 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.
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[The role of Th1, Th17, and Treg cells in the pathogenesis of rheumatoid arthritis including anti-inflammatory action of Th1 cytokines].
Postȩpy higieny i medycyny doświadczalnej (Online). 01/2011; 65:397-403.
Dysregulation in the immune system plays an important role in the pathogenesis of rheumatoid arthritis (RA). The persistent nature of arthritis strengthens the suggestion of immune dysfunction, consisting in predominance of the pro-inflammatory response. It seems that both local and systemic immune ... [more] Dysregulation in the immune system plays an important role in the pathogenesis of rheumatoid arthritis (RA). The persistent nature of arthritis strengthens the suggestion of immune dysfunction, consisting in predominance of the pro-inflammatory response. It seems that both local and systemic immune abnormalities, including PBMC secreting abnormal levels of pro- and anti-inflammatory cytokines, may be involved in the evolution of the disease. Helper T cells (Th) differentiate towards Th1, Th2, Th17, and Treg cells according to the cytokine microenvironment. Active RA results from the imbalance in distribution of functional pro-inflammatory Th17 and anti-inflammatory Treg cells. Affected Th1 cytokine secretion observed in the course of RA contributes to the increase in IL-17 production and Th17 infiltration in the synovial tissue. Current studies have demonstrated that pro-inflammatory Th1 cytokines may also exert an anti-inflammatory action on the balance between Th17 and Treg cells by promotion of Treg differentiation. In the paper, we also show the influence of TNF-alpha and its inhibitors on the distribution of Th subpopulations in RA patients.
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2.43Impact points
Zeta chain expression in T and NK cells in peripheral blood of children with nephrotic syndrome.
Pediatric nephrology (Berlin, Germany). 10/2009;
The idiopathic nephrotic syndrome (INS) has been related to cellular immune disturbances. The zeta (zeta) 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 exam... [more] The idiopathic nephrotic syndrome (INS) has been related to cellular immune disturbances. The zeta (zeta) 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.
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3.28Impact points
The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease.
Immunology. 09/2009; 128(1 Suppl):e787-96.
Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important molecule in the down-regulation of T-cell activation. A study was undertaken to evaluate the association of the CTLA-4 gene polymorphisms -319C/T, +49A/G, (AT)(n), CT60A/G and Jo31G/T with the levels of membrane CTLA-4 (mCTLA-4) and cytoplasm... [more] Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important molecule in the down-regulation of T-cell activation. A study was undertaken to evaluate the association of the CTLA-4 gene polymorphisms -319C/T, +49A/G, (AT)(n), CT60A/G and Jo31G/T with the levels of membrane CTLA-4 (mCTLA-4) and cytoplasmic CTLA-4 (cCTLA-4) in CD4(+) T lymphocytes from patients with multiple sclerosis (MS) and with susceptibility to MS, and the course of the disease. It was found that the Jo31GG and CT60GG genotypes were associated with decreased mean fluorescence intensity (MFI) of total CTLA-4 (mCTLA-4 + cCTLA-4) molecules in CD4(+) T cells from both relapsing-remitting (RR) and secondary progressive (SP) MS patients compared with others. Consequently, possessing the Jo31G allele and/or the CT60G allele were associated with susceptibility to MS. The percentages of cells expressing mCTLA-4 and cCTLA-4 in RR patients were higher in carriers of the alleles non-predisposing to MS (namely CT60A and Jo31T), but the percentages of corresponding cells were unexpectedly significantly lower in SP patients than in RR patients. Increased risk of paresthesia and pyramidal signs as a first manifestation of disease, and earlier transition to the SP form in those patients, was also noted. It is hypothesized that the decreasing frequencies of cells expressing immunosuppressive mCTLA-4 and cCTLA-4 in carriers of alleles non-predisposing to MS (i.e. CT60A and Jo31T) may lead to inadequate down-regulation of ongoing T-cell responses in these patients and, as a consequence, earlier progression of disease from the RR form to the SP form.
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1.59Impact points
Impaired zeta chain expression and IFN-gamma production in peripheral blood T and NK cells of patients with advanced lung cancer.
Oncology reports. 02/2009; 21(1):173-84.
Recent studies show that low expression of zeta chain in T and NK cell leads to impaired anti-tumour immunity in patients with cancer, poor prognosis, and shorter overall survival. Therefore, monitoring zeta chain expression may be useful in assessing immune competence in lung cancer patients and in... [more] Recent studies show that low expression of zeta chain in T and NK cell leads to impaired anti-tumour immunity in patients with cancer, poor prognosis, and shorter overall survival. Therefore, monitoring zeta chain expression may be useful in assessing immune competence in lung cancer patients and in following changes during anticancer therapies. Such studies concerning small-cell and non-small cell lung cancer (SCLC and NSCLC, respectively) have not been published so far. The expression of zeta chain and IFN-gamma in peripheral blood (PB) T and NK cells from SCLC and NSCLC patients at advanced (III, IV) stages were analysed before and after chemotherapy with etoposide and cisplatin using flow cytometry. Serum concentrations of TGF-beta1 and IL-10 were also estimated at each time point tested. Before therapy, impaired zeta chain expression was observed in all the patients corresponding with increased levels of immuno-suppressive cytokines in sera compared with controls. Decreased IFN-gamma production in T cells from all patients was also demonstrated. In NK cells, IFN-gamma was secreted at lower levels in NSCLC patients, while in the SCLC group it was normal. After chemotherapy, restoration of zeta expression in NK cells and its insignificant increase in T cells in SCLC patents corresponding with normalization of TGF-beta secretion were noted. In contrast, NSCLC patients retained impaired zeta expression in T and NK cells. SCLC and NSCLC patients showed a profound defect in IFN-gamma secretion in T and NK cells upon treatment. There were no differences in studied parameters between NSCLC and SCLC groups before and after chemotherapy. This is the first report of impaired zeta expression in PB T and NK cells in patients with SCLC and NSCLC in advanced stages, which may result from higher levels of immunosuppressive cytokines in sera. After cytostatic treatment, all the studied patients, including those with initial good response to chemotherapy, remained with profound abnormalities in T and NK cells, which could have dramatic consequences regarding severely impaired anti-tumour immunity.
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2.35Impact points
High intracellular content of cyclin-dependent kinase inhibitor p27 in early- and intermediate stage B-cell chronic lymphocytic leukemia lymphocytes predicts rapid progression of the disease.
European journal of haematology. 02/2009;
Abstract Previous studies showed that peripheral blood lymphocytes of B-cell chronic lymphocytic leukemia (B-CLL) displayed a high intracellular level of cell cycle inhibitory protein p27(Kip1). It has been suggested that its' high expression may confer them survival advantage and lead to unfavo... [more] Abstract Previous studies showed that peripheral blood lymphocytes of B-cell chronic lymphocytic leukemia (B-CLL) displayed a high intracellular level of cell cycle inhibitory protein p27(Kip1). It has been suggested that its' high expression may confer them survival advantage and lead to unfavorable prognosis, but the prognostic significance of p27(Kip1) expression for previously untreated, non-advanced stage B-CLL was not established. We studied a relationship between the intracellular level of p27(Kip1) of lymphocytes of early- and intermediate stage B-CLL patients and their spontaneous apoptosis in vitro, as well as prognostic significance of p27(Kip1) in B-CLL lymphocytes for the risk of disease progression. Intracellular p27(Kip1) content of peripheral blood lymphocytes obtained from 48 previously untreated 0-II Rai stage B-CLL patients was determined by flow cytometry. The viability and apoptosis of those lymphocytes after 72-h culture were also assessed. During the follow-up period (6-71 months, median 59.5), we recorded the time elapsed to the doubling of lymphocyte count, progression to a higher Rai stage and the appearance of indications for cytostatic treatment. The p27(Kip1) expression was neither correlated with initial lymphocyte count, CD38 expression, cell viability nor spontaneous apoptosis ratio after 72-h culture. Higher p27(Kip1) level was related to the probability of earlier occurrence of each of three above-mentioned events. We did not find a prognostic significance of in vitro cell viability nor apoptosis as to the risk of disease progression. Our results indicate that elevated intracellular p27(Kip1) level in leukemic lymphocytes of early- and intermediate stage B-CLL patients contributes to rapid progression of the disease.
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1.48Impact points
Is cyclin D2 a marker of B-cLL cell activation?
Oncology research. 01/2009; 18(2-3):127-31.
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... [more] 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.
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3.25Impact points
CD28 downregulation on CD4+ T cells is associated with age of kidney transplant recipient.
Transplant international : official journal of the European Society for Organ Transplantation. 08/2008; 21(7):661-8.
There is a growing body of evidence showing that the intensity of rejection is weaker in older kidney allograft recipients while chronic complications, but not rejection, are the main causes of graft loss. To investigate whether the age of the recipient is a factor affecting the expressions of the C... [more] There is a growing body of evidence showing that the intensity of rejection is weaker in older kidney allograft recipients while chronic complications, but not rejection, are the main causes of graft loss. To investigate whether the age of the recipient is a factor affecting the expressions of the CD28, CTLA-4, and CD40L costimulatory molecules on CD4+ T cells. Their expression levels were determined in 78 kidney transplant recipients aged 17-68 years. The expression was assessed on unstimulated and anti-CD3 antibody + IL-2-stimulated CD4+ T cells. Median time after transplantation was 20 months and median serum creatinine was 1.5 mg/dl. Significant correlations between age and CD28 expression (r = -0.4, P = 0.0004) on CD4+ T cells and between age and CTLA-4 expression after stimulation (r = 0.34, P = 0.008) were found. CD40L expression on CD4+ T cells was not affected by recipient age. The decreased expression of CD28 and enhanced expression of CTLA-4 (after stimulation) associated with age may be helpful in transplant acceptance.
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2.84Impact points
Different patterns of activation markers expression and CD4+ T-cell responses to ex vivo stimulation in patients with clinically quiescent multiple sclerosis (MS).
Journal of neuroimmunology. 10/2007; 189(1-2):137-46.
Patients with relapsing-remitting (RR) and secondary progressive (SP) forms of multiple sclerosis (MS), although in long-term clinical remission, showed different patterns of increased expressions of the activation markers: CD69, CD40L, and both membrane/surface and cytoplasmic CTLA-4 (mCTLA-4 and c... [more] Patients with relapsing-remitting (RR) and secondary progressive (SP) forms of multiple sclerosis (MS), although in long-term clinical remission, showed different patterns of increased expressions of the activation markers: CD69, CD40L, and both membrane/surface and cytoplasmic CTLA-4 (mCTLA-4 and cCTLA-4, respectively) in freshly isolated peripheral blood (PB) CD4+ T cells compared with controls. Also observed were dysregulated responses to ex vivo stimulation in both groups of MS patients accompanied by increased IFN-gamma synthesis. Our findings may suggest that the mechanisms leading to each clinical form of the disease may be heterogeneous.
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[Variable expression of CD28 costimulatory molecule and CTLA4 inhibitory molecule on peripheral blood CD4+ cells in kidney allograft recipients with and without acute graft rejection]
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 09/2006; 21(122):157-9; discussion 160.
Alloimune activation is one of the most significant post transplant events, which results in increased expression of costimulatory molecules. These molecules have been suggested to play a role in determining the outcome of immune response including graft rejection. MATERIAL AND METHODS: We examined ... [more] Alloimune activation is one of the most significant post transplant events, which results in increased expression of costimulatory molecules. These molecules have been suggested to play a role in determining the outcome of immune response including graft rejection. MATERIAL AND METHODS: We examined the CD28 and both surface and intracellular CTLA-4 expression on freshly drawn and anti-CD3+rlL-2 stimulated peripheral blood CD4+ T cells in kidney transplant recipients with acute graft rejection and with non-complicated post transplant course. Dual immunofluorescence and flow cytometry methods were used. The proportion of freshly isolated CD4+/ CTLA4 was higher in both groups of graft recipients in comparison to healthy controls reflecting in vivo allostimulation. RESULTS: We found the increased percentage of CD4+ cells expressing surface CTLA4 after stimulation, unstimulated intracellular CTLA4 and lower percentage of CD4+ cells expressing CD28 after stimulation in kidney recipients without rejection. CONCLUSIONS: Our results indicate the possible relationship between the expression pattern of CTLA4 inhibitory molecule on CD4+ cells and clinical course after renal transplantation.
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2.44Impact points
CD40L, CD28, and CTLA-4 expression on CD4+ T cells in kidney graft recipients: a relationship with post-transplantation clinical course.
Transplant immunology. 07/2006; 16(1):32-40.
BACKGROUND: Experimental studies have demonstrated that the intensity of alloreactivity against a transplanted organ results from an interaction of positive (CD40/CD40L and B.7/CD28) and inhibitory (B.7/CTLA-4) signals between antigen-presenting cells (APCs) and T lymphocytes. METHODS: We examined t... [more] BACKGROUND: Experimental studies have demonstrated that the intensity of alloreactivity against a transplanted organ results from an interaction of positive (CD40/CD40L and B.7/CD28) and inhibitory (B.7/CTLA-4) signals between antigen-presenting cells (APCs) and T lymphocytes. METHODS: We examined the CD40L, CD28, and both surface (s) and intracellular (i) CTLA-4 expressions on freshly drawn and anti-CD3+rIL-2-stimulated peripheral blood CD4+ T cells in groups of kidney transplant recipients in relation to distinct clinical course using the tri-color immunofluorescence method. RESULTS: The median proportions of freshly isolated CD3+/CD4+/CTLA-4+ and CD3+/CD4+/CD40L+ cells in all groups of graft recipients were higher than in control subjects. In patients with stable graft function (SGF), non-significantly higher sCTLA-4, significantly higher iCTLA-4 expression, and significantly lower CD40L expression on freshly drawn CD4+ T cells compared with recipients with chronic allograft nephropathy (CAN) were found. Moreover, CD4+ T cells from SGF patients showed a higher potential to express sCTLA-4 and CD40L molecules and to down-regulate the CD28 molecule in response to ex vivo stimulation than those from patients with CAN. In patients without acute graft rejection (NAGR), a markedly higher proportion of freshly drawn CD3+/CD4+/iCTLA-4+ cells compared with patients with acute graft rejection (AGR) and an up-regulation of the median percentage of CD3+/CD4+/CD40L+ cells after ex vivo stimulation was found. CONCLUSIONS: In patients with SGF, peripheral blood CD4+ T cells exhibited a higher potential to express surface CTLA-4 and CD40L and to down-regulate CD28 costimulatory molecules in response to ex vivo stimulation, indicating a relationship between the expression patterns of both costimulatory and inhibitory molecules in CD4+ T cells and clinical course after renal transplantation.
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[Expression of zeta (zeta) chain in peripheral blood T lymphocytes and NK cells of children with idiopathic nephrotic syndrome (INS)--preliminary results]
Przegla̧d lekarski. 02/2006; 63 Suppl 3:208-10.
Cellular immune disturbances have been implicated in the pathogenesis of idiopathic nephrotic syndrome. The zeta (zeta) chain, which is a component of the TCR/CD3 complex and CD16 heterodimer in NK cells, plays a crucial role in signal transducing events leading to T and NK cell activation and proli... [more] Cellular immune disturbances have been implicated in the pathogenesis of idiopathic nephrotic syndrome. The zeta (zeta) chain, which is a component of the TCR/CD3 complex and CD16 heterodimer in NK cells, plays a crucial role in signal transducing events leading to T and NK cell activation and proliferation. The aim of our study was to examine the zeta (zeta) chain expression in peripheral blood CD4+, CD8+ T-lymphocytes and NK cells (CD3-/CD56+) derived from children with NS in active phase of the disease and in remission. We also examined the effect of 24 and 72 h anti-CD3+rIL-2 stimulation on the zeta chain expression in all studied groups. MATERIAL AND METHODS: The study group consisted of 8 children with INS in active phase of the disease, 11 children with INS in clinical remission and 15 age-matched healthy controls. The level of zeta (zeta) chain expression, assessed by flow cytometry, was determined as the mean fluorescence intensity (MFI). RESULTS: In INS patients with active phase MFI values for CD4+ cells were higher than in children with remission and in controls. The levels of zeta in CD4+ T-lymphocytes of patients with remission were comparable to those in controls. There were no differences between zeta levels on NK cells in examined groups. Ex vivo stimulation had no impact on zeta expression in children with acute phase of NS, whereas in patients on remission stimulation with anti-CD3+rIL-2 increased zeta expression on CD4+ cells and decreased it on NK cells. NK zeta expression was also diminished in the control group. CONCLUSIONS: Preliminary results point at the alterations of zeta expression in children with INS as a probable cause of immune dysregulation in this group of patients.
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[CD40L expression on T CD4+ lymphocytes from peripheral blood in patients with relapsing-remitting and secondary progressive multiple sclerosis]
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 02/2006; 20(115):41-5.
Multiple sclerosis (MS) is believed to be a T cell-mediated autoimmune disease. One of the particularly important signals is mediated by CD40L, a costimulatory molecule which appears on activated T cell. The aim of this study was examination of the CD40L expression on freshly obtained lymphocytes T ... [more] Multiple sclerosis (MS) is believed to be a T cell-mediated autoimmune disease. One of the particularly important signals is mediated by CD40L, a costimulatory molecule which appears on activated T cell. The aim of this study was examination of the CD40L expression on freshly obtained lymphocytes T CD4+ which were ex vivo stimulated with monoclonal antibody anti CD3+rIL-2 in patients with relapsing-remitting and secondary progressive multiple sclerosis. MATERIAL AND METHODS: 12 relapsing-remitting (RR) and 16 secondary progressive (SP) MS patients with long-lasting clinical remission and 24 healthy subjects were included in the study. The proportion of unstimulated and ex vivo stimulated with anti CD3+rIL-2 TCD4+ cells from peripheral blood co-expressing CD40L was studied by dual immunofluorescence method. RESULTS: The proportion of unstimulated and stimulated T CD4+CD40L+ cells did not differ significantly between RRMS and controls. The percentage of unstimulated TCD4+CD40L+ cells from SP patients exhibited significantly higher proportion - when compared with controls. These cells did not respond to ex vivo stimulation and their level was similar to that of stimulated cells from controls. CONCLUSION: Dysregulation of costimulation in SPMS expressing as enhanced percentage of TCD4+CD40L+ cells may be responsible for maintenance of chronic activation state of lymphocytes leading to prolonged inflammatory process.
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8.30Impact points
CTLA-4 overexpression in CD19+/CD5+ cells correlates with the level of cell cycle regulators and disease progression in B-CLL patients.
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 03/2005; 19(2):301-4.
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1.61Impact points
Carp liver DNase--isolation, further characterization and interaction with endogenous actin.
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 02/2005; 140(1):141-51.
Deoxyribonuclease I (DNase I)-like enzyme from the liver of the carp (Cyprinus carpio) was purified to homogeneity and further characterized. Ion exchange chromatography on DEAE-cellulose, molecular filtration on Sephacryl S-300 and Con A-Sepharose affinity chromatography were applied for enzyme iso... [more] Deoxyribonuclease I (DNase I)-like enzyme from the liver of the carp (Cyprinus carpio) was purified to homogeneity and further characterized. Ion exchange chromatography on DEAE-cellulose, molecular filtration on Sephacryl S-300 and Con A-Sepharose affinity chromatography were applied for enzyme isolation. Carp liver DNase, similarly to DNase I from bovine pancreas, was found to be an endonuclease that hydrolyses linear DNA from salmon sperm as well as circular DNA forms--plasmid and cosmid. The purified enzyme is a glycoprotein and shows microheterogeneity, as observed in DNase zymograms prepared after native and two-dimensional electrophoresis (2D-PAGE). The composition of sugar component of the enzyme was characterized. Special attention was focused on the ability of carp liver DNase to interact with carp liver actin. The carp liver enzyme was inhibited by endogenous actin. The estimated binding constant of carp liver DNase to carp liver actin was calculated to be 1.1 x 10(6) M(-1).
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[Plasma concentration of the shed form of L-selectin (sL-selectin) in patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL) and its relation to the clinical course]
Polskie archiwum medycyny wewnȩtrznej. 12/2004; 112(5):1283-8.
L-selectin plays a critical role in the initiation of normal leukocyte attachment to activated endothelium. It is expressed on most normal leukocytes and is also detectable on blast cells in ALL and AML. The shed form of L-selectin (sL-selectin) is found in plasma. High plasma sL-selectin levels wer... [more] L-selectin plays a critical role in the initiation of normal leukocyte attachment to activated endothelium. It is expressed on most normal leukocytes and is also detectable on blast cells in ALL and AML. The shed form of L-selectin (sL-selectin) is found in plasma. High plasma sL-selectin levels were detectable in patients with AML and correlated with disease activity and poor prognosis. Little information is available on the clinical and prognostic significance of sL-selectin in ALL. The study was undertaken to determine sL-selectin levels during clinical course of patients with ALL and AML and to assess its role as a disease activity and prognostic factor. Heparinized plasma was obtained from 83 patients with newly diagnosed acute leukemia, including 30 with ALL, 50 with AML, 3 with biphenotypic leukemia and 19 healthy people. For some patients additional samples were taken in complete remission (CR) and relapse. sL-selectin was assayed using an ELISA method. The mean plasma sL-selectin concentration in all patients with acute leukemia was significantly higher than and in normals. Concentration of s-selectin L in patients with CR was significantly lower than at presentation and in the range of normals. sL-selectin plasma concentration in relapse was comparable to that from diagnosis. There was no significant difference in sL-selectin concentration between patients who entered CR after induction treatment and without CR. Patients with extramedullary disease had higher sL-selectin than patients without that manifestation. Monitoring of the sL-selectin concentration maybe useful for evaluating leukemia activity in both ALL and AML patients.
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4.35Impact points
Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia.
British journal of cancer. 06/2004; 90(10):2042-8.
In the present study, we have examined the kinetics and magnitude of expression of the CD28 and CD152 molecules on unstimulated and anti-CD3+rIL-2-stimulated peripheral blood CD4+ and CD8+ T cells in patients with chronic lymphocytic leukaemia (B-CLL) and controls. The mean percentages of both CD3+/... [more] In the present study, we have examined the kinetics and magnitude of expression of the CD28 and CD152 molecules on unstimulated and anti-CD3+rIL-2-stimulated peripheral blood CD4+ and CD8+ T cells in patients with chronic lymphocytic leukaemia (B-CLL) and controls. The mean percentages of both CD3+/CD4+/CD28+ and CD3+/CD8+/CD28+ cells were significantly lower in B-CLL than in controls before culture, decreased rapidly, reaching their lowest levels between 24 and 48 h, and returned to basal levels after 72 h of culture. In controls, the lowest proportions of CD3+/CD4+/CD28+ and CD3+/CD8+/CD28+ cells were found after 24 h and returned to prestimulation levels after 48 h of stimulation. We observed significantly higher proportions of unstimulated CD3+/CD4+/CD152+ and CD3+/CD8+/CD152+ cells in B-CLL patients than in controls. The highest percentages of CD3+/CD4+/CD152+ and CD3+/CD8+/CD152+ cells were observed in controls after 72 h, and in B-CLL patients after 24 h, and remained statistically higher after 48, 72 and 96 h of stimulation. CD152 molecule expression returned to prestimulation levels after 96 h of culture in controls, and after 120 h in B-CLL patients. The abnormal kinetics and levels of CD28 and CD152 expression on T cells in B-CLL may lead to a state of hyporesponsiveness or anergy and could be one of the mechanisms of immune deficiency in this disease.
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4.60Impact points
Correlation of blood lymphocyte CTLA-4 (CD152) induction in Hodgkin's disease with proliferative activity, interleukin 2 and interferon-gamma production.
British journal of haematology. 08/2002; 118(1):202-9.
Expression of the downregulatory CTLA-4 molecule was determined on unstimulated and anti-CD3 + recombinant interleukin 2 (rIL-2)-stimulated peripheral blood T cells in Hodgkin's disease (HD) and correlated with the T-cells' proliferative activity, IL-2 and interferon (IFN)-gamma production. ... [more] Expression of the downregulatory CTLA-4 molecule was determined on unstimulated and anti-CD3 + recombinant interleukin 2 (rIL-2)-stimulated peripheral blood T cells in Hodgkin's disease (HD) and correlated with the T-cells' proliferative activity, IL-2 and interferon (IFN)-gamma production. There was a negligible percentage of CTLA-4+/CD3+ cells before culture. The mean percentage of CTLA-4+/CD3+ lymphocytes increased gradually, peaked after 72 h of stimulation and returned to basal values after 96 h of stimulation. The mean proportion of CTLA-4+/CD3+ cells from untreated patients was significantly higher after 24, 48 and 72 h of stimulation compared with controls. The mean percentage of CTLA-4+/CD3+ cells from patients in clinical remission (CR) was lower than that of untreated patients, but remained significantly higher compared with controls. Lymphocytes from untreated HD patients showed impaired proliferative activity, IL-2 and IFN-gamma production compared with controls. The proliferative activity of the lymphocytes, IL-2 and IFN-gamma production remained significantly lower in CR compared with controls. The proportion of CTLA-4+/CD3+ cells negatively correlated with proliferative activity, IL-2 and IFN-gamma production in HD patients and controls. However, some untreated patients as well as patients in CR with normal mean fluorescence intensity values of CTLA-4 showed unimpaired T-cell function tests. Our study provides the first evidence of an increased expression of downregulatory CTLA-4 molecule on stimulated T-cells in HD, which could be one of the mechanisms of immune deficiency in this disease.
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1.99Impact points
CD28 costimulatory molecule--expression, structure and function.
Archivum immunologiae et therapiae experimentalis. 02/2002; 50(3):169-77.
T cell activation is a key event in triggering an antigen specific immune response of the organism. The process is induced primarily by the signal generated by direct interaction of a T cell receptor with an antigen bound to the major histocompatibile complex on an antigen-presenting cell (APC). Alt... [more] T cell activation is a key event in triggering an antigen specific immune response of the organism. The process is induced primarily by the signal generated by direct interaction of a T cell receptor with an antigen bound to the major histocompatibile complex on an antigen-presenting cell (APC). Although the signal is critical in exciting immune response, an additional, costimulating signal is required. The major second signal is generated by interaction of the CD28 molecule expressed on most T lymphocytes with its natural ligands CD80 and CD86 located on APCs. The signal excited by CD28 triggering involves multiple second-messenger cascades, leading to the activation of transcription factors and finally results in cell proliferation, cytokine production, and the generation of effector functions. The importance of CD28-delivered costimulatory signals was proven in experiments with CD28-deficient mice. T cells from these mice exhibited an impaired pattern of cytokine secretion and defects in T cell-dependent antibody production. Certain forms of immunopathology might result from the aberrant regulation of CD28 expression.
Following (3)
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Marcin Wojtowicz
Regional Hospital in Opole -
Piotr Kusnierczyk
Ludwik Hirszfeld Institute of Immunology and Experimental Therapy -
Lidia Karabon
instytut Immunologii i Terapii Doświadczalnej PAN
