Biomedical subjects

Agata Kosmaczewska

Publications and source records attributed to Agata Kosmaczewska.

6 recordsLinked to original sources

PubMed2006

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

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.

Adolescent↗

PubMed2006

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

UNLABELLED: 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.

Adult↗

PubMed2006

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

UNLABELLED: 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.

Adolescent↗

PubMed2006

[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].

UNLABELLED: 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.

Acute Disease↗

PubMed2002

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

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.

Abatacept↗

PubMed2002

CD28 costimulatory molecule--expression, structure and function.

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.

Adaptor Proteins, Signal Transducing↗