Biomedical subjects

Dorota Boćko

Publications and source records attributed to Dorota Boćko.

3 recordsLinked to original sources

PubMed2003

Lack of association between an exon 1 CTLA-4 gene polymorphism A(49)G and multiple sclerosis in a Polish population of the Lower Silesia region.

Multiple sclerosis (MS) a chronic inflammatory demyelinating disease of the central nervous system is believed to have a T cell-mediated autoimmune etiology. The cytotoxic T lymphocyte antigen 4 (CTLA-4) gene is a strong candidate for the involvement in autoimmune diseases because CTLA-4 plays an important role in the downregulation of the early and late stages of T cell activation and the maintenance of peripheral T cell tolerance. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed an exon 1 CTLA-4 gene polymorphism A(49)G in 102 unrelated Polish MS patients in the Lower Silesia region and 101 age- and sex-matched healthy subjects. The distribution of CTLA-4 exon 1 A(49)G genotype, phenotype and allele frequencies did not differ between patients with MS and healthy subjects.

Adult↗

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↗