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Apoptosis Signaling Is Altered in CD4(+)CD25(+)FoxP3(+) T Regulatory Lymphocytes in Pre-Eclampsia
Authors:Dorota Darmochwal-Kolarz  Shigeru Saito  Jacek Tabarkiewicz  Bogdan Kolarz  Jacek Rolinski  Bozena Leszczynska-Gorzelak  Jan Oleszczuk
Affiliation:Department of Obstetrics and Perinatology, Medical University of Lublin, Lublin 20-950, Al. Raclawickie 1, Poland; E-Mails: b.leszczynska@umlub.pl (B.L.-G.); jan.oleszczuk@umlub.pl (J.O.).
Abstract:The aim of our study was to estimate the surface expressions of CD95 (APO-1/Fas) antigen and the intracellular expressions of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax in CD4(+)CD25(+)FoxP3(+) T regulatory lymphocytes (Tregs) as well as the percentage of CD8(+)CD28(+) T cytotoxic cells in peripheral blood of patients with pre-eclampsia in comparison with healthy pregnant women in the third trimester of physiological pregnancy. Twenty-four women with pre-eclampsia and 20 normal third trimester pregnant women were included in the study. The lymphocytes were isolated from peripheral blood samples and labeled with monoclonal antibodies. The expressions of surface antigens and intracellular proteins were estimated using flow cytometry. The population of CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower in peripheral blood of patients with pre-eclampsia when compared to normal third trimester pregnant women. The percentages of CD4(+)CD25(+)FoxP3(+) Treg cells that express Bcl-2 protein were significantly lower in peripheral blood of patients with pre-eclampsia when compared to healthy pregnant women, whereas the percentages of CD4(+)CD25(+)FoxP3(+) Treg cells with the expressions of Bax protein did not differ in both groups. Moreover, the mean fluorescence intensity (MFI) of Bcl-2 protein in CD4(+)CD25(+)FoxP3(+) Treg cells was significantly lower and MFI of Bax protein significantly higher in pre-eclampsia when compared to the control group. The percentage of CD8(+)CD28(+) T cells did not differ in both studied groups but MFI of CD28 antigen on T CD8(+) cells was significantly higher in pre-eclampsia when compared to the control group. The obtained results suggest that the deficit of CD4(+)CD25(+)FoxP3(+) Treg lymphocytes which is observed in pre-eclampsia may be associated with altered apoptosis signaling in Tregs.
Keywords:apoptosis  Bax protein  Bcl-2 protein  CD95 antigen  pre-eclampsia  pregnancy  Treg cells
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