Agata Kosmaczewska

Publications of Agata Kosmaczewska

• 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.

  Authors: Agata Kosmaczewska, Dorota Bocko, Lidia Ciszak, Iwona Wlodarska-Polinska, Jan Kornafel, Aleksandra Szteblich, Anna Masternak, Irena Frydecka

  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.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.

• [The role of Th1, Th17, and Treg cells in the pathogenesis of rheumatoid arthritis including anti-inflammatory action of Th1 cytokines].

  Authors: Agata Kosmaczewska, Jerzy Swierkot, Lidia Ciszak, Piotr Wiland

  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,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.

• Zeta chain expression in T and NK cells in peripheral blood of children with nephrotic syndrome.

  Authors: Kinga Musiał, Lidia Ciszak, Agata Kosmaczewska, Aleksandra Szteblich, Irena Frydecka, Danuta Zwolińska

  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,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.

• The CTLA-4 gene polymorphisms are associated with CTLA-4 protein expression levels in multiple sclerosis patients and with susceptibility to disease.

  Authors: Lidia Karabon, Agata Kosmaczewska, Malgorzata Bilinska, Edyta Pawlak, Lidia Ciszak, Anna Jedynak, Anna Jonkisz, Leszek Noga, Anna Pokryszko-Dragan, Magdalena Koszewicz, Irena Frydecka

  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 polymorphismsCytotoxic 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.

• Impaired zeta chain expression and IFN-gamma production in peripheral blood T and NK cells of patients with advanced lung cancer.

  Authors: Lidia Ciszak, Agata Kosmaczewska, Bozena Werynska, Aleksandra Szteblich, Renata Jankowska, Irena Frydecka

  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,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.

• 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.

  Authors: Dariusz Wolowiec, Marcin Wojtowicz, Lidia Ciszak, Agata Kosmaczewska, Irena Frydecka, Stanislaw Potoczek, Donata Urbaniak-Kujda, Katarzyna Kapelko-Slowik, Kazimierz Kuliczkowski

  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). ItAbstract 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.

• Is cyclin D2 a marker of B-cLL cell activation?

  Authors: Agata Kosmaczewska, Lidia Ciszak, Aleksandra Szteblich, Anna Laba, Marcin Wojtowicz, Dariusz Wolowiec, Irena Frydecka

  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 isolatedThe 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.

• CD28 downregulation on CD4+ T cells is associated with age of kidney transplant recipient.

  Authors: Mariusz Kusztal, Agata Kosmaczewska, Maria Magott-Procelewska, Irena Frydecka, Lidia Ciszak, Dorota Bocko, Dariusz Patrzalek, Marian Klinger

  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 graftThere 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.

• [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]

  Authors: Maria Magott-Procelewska, Agata Kosmaczewska, Irena Frydecka, Lidia Ciszak, Dariusz Patrzałek, Piotr Szyber, Marian Klinger

  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 inAlloimune 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.

• CD40L, CD28, and CTLA-4 expression on CD4+ T cells in kidney graft recipients: a relationship with post-transplantation clinical course.

  Authors: Agata Kosmaczewska, Maria Magott-Procelewska, Irena Frydecka, Lidia Ciszak, Dorota Bocko, Aleksandra Szteblich, Piotr Kusnierczyk, Dariusz Patrzalek, Piotr Szyber, Marian Klinger

  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 inhibitoryBACKGROUND: 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.

• [Expression of zeta (zeta) chain in peripheral blood T lymphocytes and NK cells of children with idiopathic nephrotic syndrome (INS)--preliminary results]

  Authors: Kinga Musiał, Lidia Ciszak, Agata Kosmaczewska, Aleksandra Szteblich, Edyta Pawlak, Danuta Zwolińska, Irena Frydecka

  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 NKCellular 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.

• [CD40L expression on T CD4+ lymphocytes from peripheral blood in patients with relapsing-remitting and secondary progressive multiple sclerosis]

  Authors: Małgorzata Bilińska, Irena Frydecka, Agata Kosmaczewska, Lidia Ciszak, Magdalena Koszewicz, Anna Pokryszko-Dragan

  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 TMultiple 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.

• Correlation of blood lymphocyte CTLA-4 (CD152) induction in Hodgkin's disease with proliferative activity, interleukin 2 and interferon-gamma production.

  Authors: Agata Kosmaczewska, Irena Frydecka, Dorota Boćko, Lidia Ciszak, Renata Teodorowska

  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) andExpression 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.

• CD28 costimulatory molecule--expression, structure and function.

  Authors: Dorota Boćko, Agata Kosmaczewska, Lidia Ciszak, Renata Teodorowska, Irena Frydecka

  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 receptorT 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.

• The significance of Treg cells in defective tumor immunity.

  Authors: Agata Kosmaczewska, Lidia Ciszak, Stanisław Potoczek, Irena Frydecka

  Archivum immunologiae et therapiae experimentalis. 56(3):181-91.

  Regulatory T cells (Treg) enriched in FoxP3+, glucocorticoid-induced TNF receptor+, and cytotoxic T-lymphocyte-associated antigen-4+ exert a potential to suppress effector T cells in the periphery.Regulatory T cells (Treg) enriched in FoxP3+, glucocorticoid-induced TNF receptor+, and cytotoxic T-lymphocyte-associated antigen-4+ exert a potential to suppress effector T cells in the periphery. These cells exist in markedly higher proportions within tumor-infiltrating lymphocytes, peripheral blood lymphocytes, and/or regional lymph node lymphocytes of patients with cancer and their frequencies are suggested to be strongly related to tumor progression and inversely correlated with the efficacy of treatment. Tumor-specific Treg cells require ligand-specific activation and cell-to-cell contact to exert their suppressive activity on tumor-specific effector cells (CD8+ cytotoxic T lymphocytes and CD4+ Th cells), which includes decreased cytotoxity, proliferation, and Th1 cytokine secrection. Depletion or blockade of Treg cells can enhance immune protection from tumor-associated antigens that are expressed as self antigens. Recent studies revealed that lymphoma T cells might adopt a Treg profile as well. Studies assessing the influence of chemotherapy on Treg cells have also been included in this review.

• Alterations in the expression of signal-transducing CD3 zeta chain in T cells from patients with chronic inflammatory/autoimmune diseases.

  Authors: Lidia Ciszak, Edyta Pawlak, Agata Kosmaczewska, Stanisław Potoczek, Irena Frydecka

  Archivum immunologiae et therapiae experimentalis. 55(6):373-86.

  The CD3 zeta chain, a component of the T cell receptor (TCR)/CD3 complex, is considered to be a limiting factor in the assembly and transport of the TCR/CD3 complex to the cell surface and is crucialThe CD3 zeta chain, a component of the T cell receptor (TCR)/CD3 complex, is considered to be a limiting factor in the assembly and transport of the TCR/CD3 complex to the cell surface and is crucial to receptor signaling function. Recent studies have demonstrated altered expression and function of this signal transduction molecule in T and natural killer cells in patients with chronic inflammatory/autoimmune diseases. In this review, current knowledge concerning the expression of CD3 zeta chain as well as the mechanisms responsible for abnormal expression of this molecule in systemic lupus erythematosus, rheumatoid arthritis, and childhood idiopathic nephrotic syndrome are summarized.