Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia?
ABSTRACT Regulatory T cells (CD4(+)CD25(+)FoxP3(+)-Treg cells) are important regulators of tolerance induction during pregnancy. We now found that the number of CD4(+)CD25(+)FoxP3(+)-Treg cells decreases during normal course of pregnancy and even more so in women affected by preeclampsia. The functional activity of these CD4(+)CD25(+)-Treg cells was significantly reduced in comparison to those of healthy pregnants. Further analysis revealed two Treg subsets that differed with regard to the FoxP3 and CD25 expression. The percentage of both, CD4(+)CD25(+)FoxP3(high+)-Treg and CD4(+)CD25(high+)FoxP3(+), was maximal in the first and second trimenon, but declined severely in the third trimenon. In preeclamptic women the population of CD4(+)CD25(high+)FoxP3(+)-Treg cells was particularly apparent, while the population of CD4(+)CD25(+)FoxP3(high+)-Treg cells was significantly decreased. We propose that CD4(+)CD25(+)FoxP3(high+)- and CD4(+)CD25(high+)FoxP3(+)-Treg cell populations represent distinct Treg cell subsets, and that disturbances in the balance of these two Treg cell subsets are associated with the presence of preeclampsia, but not HELLP-syndrome.
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ABSTRACT: CD4(+) CD25(bright) regulatory T (T(reg)) cells have been identified as a principle regulator of tolerance during pregnancy. In the setting of pre-eclampsia, however, little is known about the dynamics of these cells. In the current study, we determined CD4(+) CD25(bright) T(reg) cells in the peripheral blood using flow cytometry and forkhead box P3 (FoxP3(+)) cells at the placental bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC) of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non-pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were included. We found the percentage of CD25(bright) cells within the CD4(+) T cell population in PBMC was reduced significantly in both Japanese and Polish pre-eclamptic cases than in normal pregnancy subjects (P < 0.001) and non-pregnant healthy controls (P < 0.001). Also, the percentage of FoxP3(+) cells within CD3(+) T cells in the placental bed biopsy samples of pre-eclamptic cases were decreased compared to those in normal pregnancy subjects. These findings suggest that a decreased number of T(reg) cells was present in pre-eclampsia, and these changes might break the maternal tolerance to the fetus.Clinical & Experimental Immunology 07/2007; 149(1):139-45. · 3.41 Impact Factor
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ABSTRACT: CD4(+)CD25(+)FoxP3(+) regulatory T cells (T(reg)) suppress T cell function and protect rodents from autoimmune disease. Regulation of T(reg) during an immune response is of major importance. Enhanced survival of T(reg) is beneficial in autoimmune disease, whereas increased depletion by apoptosis is advantageous in cancer. We show here that freshly isolated FACS-sorted T(reg) are highly sensitive toward CD95-mediated apoptosis, whereas other T cell populations are resistant to CD95-induced apoptosis shortly after isolation. In contrast, TCR restimulation of T(reg) in vitro revealed a reduced sensitivity toward activation-induced cell death compared with CD4(+)CD25(-) T cells. Thus, the apoptosis phenotype of T(reg) is unique in comparison to other T cells, and this might be further explored for novel therapeutic modulations of T(reg).The Journal of Immunology 08/2005; 175(1):32-6. · 5.52 Impact Factor
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ABSTRACT: The association between autoimmunity and pulmonary arterial hypertension (PAH) has been appreciated for >40 yrs, but how autoimmune injury might contribute to the pathogenesis of this disease has only been examined in a case-specific manner. It is becoming increasingly clear that a variety of diverse clinical diseases, ranging from viral infections to connective tissue disorders, can culminate in pulmonary vascular pathology that is indistinguishable. Is there a hitherto unappreciated biology that unites these seemingly unrelated conditions? The answer to this question may come from the increasing body of evidence concerned with the central importance of regulatory T-cells in preventing inappropriate B-cell activity. Two striking similarities between conditions associated with severe angioproliferative pulmonary hypertension are a defect in the CD4 T-cell compartment and auto-antibody production. Pathogenic auto-antibodies targeting endothelial cells are capable of inducing vascular endothelial apoptosis and may initiate the development of PAH. The present review will focus on what is known about autoimmune phenomena in pulmonary arterial hypertension patients, in order to better consider whether an early loss of self-tolerance followed by autoimmune injury could influence the early development of severe angioproliferative pulmonary hypertension.European Respiratory Journal 12/2005; 26(6):1110-8. · 6.36 Impact Factor