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Monocytes in children with leukemias and lymphomas - down-regulation of HLA and costimulatory molecules.

100%

Łuczyński W., Stasiak-Barmuta A., Krawczuk-Rybak M., Szymański M., Malinowska I., Mitura-Lesiuk M.

vol. 51

issue 4

1067-1073

The aim of the study was to evaluate the function of monocytes in children with leukemias and lymphomas based on the expression of critical costimulatory, activatory and adhesion molecules (CD80, CD86, HLA-DR and CD54 = ICAM-1), estimated with tricolor flow cytometry. In comparison to the control group we found a lower percentage of monocytes with costimulatory molecules (CD80 before and CD86 after lipopolysaccharide stimulation) at the time of diagnosis and of monocytes with HLA-DR molecules after remission induction. We also noted a lower percentage of monocytes with HLA-DR expression in the group with severe or therapy resistant infections. The results of our investigation suggest some defect in costimulation and antigen presentation in lymphoproliferative diseases in children.

CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells

84%

Łuczyński W., Stasiak-Barmuta A., Iłendo E., Krawczuk-Rybak M., Malinowska I., Mitura-Lesiuk M., Parfieńczyk A., Szymański M.

2006

vol. 53

issue 2

377-382

Despite the very high percentage of long-term remissions in acute lymphoblastic leukemia (ALL) in children, some of them suffer from recurrence of the disease. New treatment modalities, e.g. effective geno- and immunotherapy are needed. The use of neoplasmatic cells to present tumor antigens is one of the approaches in cancer vaccines. ALL cells lack the expression of costimulatory molecules and are poor antigen presenting cells (APCs) for T-cell activation. CD40/40L interaction stimulates B-cells to proliferate, differentiate, upregulate costimulatory molecules and increase antigen presentation. The aim of the study was to test the hypothesis that ALL cells can be turned into professional APCs by CD40L activation. Children with B-cell precursor ALL were enrolled into the study. Mononuclear cells from bone marrow or peripheral blood were stimulated with CD40L and interleukin 4. Results: 1) after culture we noted upregulation of all assessed costimulatory, adhesion and activatory molecules i.e. CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II; 2) CD40L activated ALL cells induced proliferation of allogeneic T-cells (measured by [3H]thymidine incorporation). These results confirm the possibility of enhancing the immunogenicity of ALL cells with the CD40L system and indicate that this approach can be used in immunotherapeutic trials.

Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes

84%

Łuczyński W., Wawrusiewicz-Kurylonek N., Stasiak-Barmuta A., Urban R., Iłendo E., Urban M., Hryszko M., Krętowski A., Górska M.

Diabetes mellitus is one of the most common chronic diseases in children. T regulatory cells (Tregs) modulate response to autoantigens and probably play a role in pathogenesis of type 1 diabetes (T1DM). The aim of the present study was the assessment of T regulatory cells including their percentages and expression of critical genes in these cells in children with newly diagnosed type 1 diabetes. The examined group consisted of 50 children with T1DM. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD4, anti-CD25 and anti-CD127 (=IL-7R). Additionally, T regulatory cells were isolated for assessment of mRNA levels for chosen genes with the real-time RT-PCR technique. The percentages of CD4+CD25highCD127dim/- were very low and did not differ between T1DM and control children. We did not observe any statistically significant differences between healthy and diabetic children in mRNA expression for FoxP3, IL-7R (CD127), IL-8RA, IL-10RA, IL-12A, IL-2RA (CD25), IL-21, STAT1, STAT3, SOCS2, SOCS3, TGF-β1-R1, TGF-β-R2 and TBX-21 genes. Interestingly the mRNA level for CTLA-4, ICOS1, IL-23, IL-27, SMAD3 and GITR were lower in Treg cells of children with diabetes compared to the control patients. No disturbances in the percentages of T regulatory cells in patients with diabetes but diminished expression of some elements important in Treg function could be the result of an immunologic imbalance accompanying the onset of the diabetes. The results of our study should be used in future research in the field of immunotherapy in pediatric diabetes.

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3 Acta Biochimica Polonica

1 2009

1 2006

1 2004

3 Stasiak-Barmuta A.

3 Łuczyński W.

2 Iłendo E.

2 Krawczuk-Rybak M.

2 Malinowska I.

2 Mitura-Lesiuk M.

2 Szymański M.

1 Górska M.

1 Hryszko M.

1 Krętowski A.

1 Parfieńczyk A.

1 Urban M.

1 Urban R.

1 Wawrusiewicz-Kurylonek N.

Search results

Monocytes in children with leukemias and lymphomas - down-regulation of HLA and costimulatory molecules.

CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells

Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes