0000000000142565
AUTHOR
Andrea Steinborn
The extent of HLA-DR expression on HLA-DR+Tregs allows the identification of patients with clinically relevant borderline rejection
Regulatory T cells (Tregs) were shown to be involved into the pathogenesis of acute rejection after transplantation. The suppressive activity of the total regulatory T cell pool depends on its percentage of highly suppressive HLA-DR(+) -Treg cells. Therefore, both the suppressive activity of the total Treg pool and the extent of HLA-DR expression of HLA-DR(+) -Tregs (MFI HLA-DR) were estimated in non transplanted volunteers, patients with end-stage renal failure (ESRF), healthy renal transplant patients with suspicion on rejection, due to sole histological Bord-R or sole acute renal failure (ARF), and patients with clinically relevant borderline rejection (Bord-R and ARF). Compared to patie…
A distinct subset of HLA-DR+-regulatory T cells is involved in the induction of preterm labor during pregnancy and in the induction of organ rejection after transplantation.
Regulatory T cells (Tregs) are known to suppress alloimmune responses during pregnancy and post organ transplantation. We demonstrate that a distinct subset of FoxP3(+)DR(+)-Tregs among the total CD4(+)CD127(low+/-)CD25(+)-Treg cell pool is critically involved in preterm labor induction and kidney transplant rejection as well. Compared to healthy pregnancies and non-rejecting kidney recipients, we found that the percentage of the FoxP3(+)DR(+)-Treg subset was not reduced, but that the level of HLA-DR expression of such Tregs was strongly diminished in preterm laboring women and in patients with acute renal allograft rejection. In addition, both patient collectives showed a significantly red…
The role of recent thymic emigrant-regulatory T-cell (RTE-Treg) differentiation during pregnancy.
During pregnancy, regulatory T cells (Tregs) have a key role in maternal immune tolerance to the semi-allogeneic fetus. Our previous results showed that the naive CD45RA(+)-Treg pool is functionally improved in pregnant women compared with non-pregnant women. Therefore, we examined the thymic output and differentiation of CD45RA(+)CD31(+) recent thymic emigrant (RTE)-Tregs during normal pregnancy and in the presence of preeclampsia. With the onset of pregnancy, the composition of the total CD4(+)CD127(low+/-)FoxP3(+)-Treg pool changed in the way that its percentage of RTE- and CD45RA(-)CD31(+)-memory Tregs decreased strongly, whereas that of the CD45RA(+)CD31(-)-mature naive (MN)-Tregs did …
The Presence of Gestational Diabetes is Associated with Increased Detection of Anti-HLA-class II Antibodies in the Maternal Circulation
Problem Gestational diabetes (GD) may be associated with temporarily reduced immune tolerance toward alloantigens for the time of pregnancy. The aim of this study was to assess anti-HLA-class I and -II antibodies as markers for an aberrant immunostimulation in women with GD. Method of study The percentage of anti-HLA-class I and -II antibodies was estimated in women with GD, normal term delivery and fetal distress, which was confirmed by demonstrating low cord blood pH for this patient group. These antibodies may cross the placental barrier and cause interleukin-6 (IL-6) release from fetal monocytes by cross-linking monocytes with antibody-loaded cells. Therefore we estimated the percentage…
Small for gestational age (SGA) neonates show reduced suppressive activity of their regulatory T cells
Little information exists concerning the role of fetal regulatory T cells (Tregs) during intrauterine development. We examined whether complications such as reduced birth weight or the occurrence of preterm labor were associated with deficiencies in the number or in the immunosuppressive activity of Tregs in the fetal circulation. Their total number did not change during normal or complicated pregnancy. In contrast, their level of FoxP3 expression decreased continuously with gestational age and was significantly reduced in the presence of spontaneous term, but not preterm labor. In small for gestational age (SGA) neonates, FoxP3 expression was constantly decreased when compared to age match…
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. …
Pregnancy-associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs
Dysregulations concerning the composition and function of regulatory T cells (T(regs)) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3)(+) T(reg) cell pool contains four distinct T(reg) subsets: DR(high+) CD45RA(-), DR(low+) CD45RA(-), DR(-) CD45RA(-) T(regs) and naive DR(-) CD45RA(+) T(regs). During the normal course of pregnancy, the most prominent changes in the composition of the total T(reg) cell pool were observed between the 10th and 20th weeks of gestation, with a clear decrease in the percentage of DR(high+) CD45RA(-) and…
The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus.
Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3(+)) T(reg) pool consists of four different T(reg) subsets: naive CD45RA(+) T(regs), HLA-DR(-) CD45RA(-) memory T(regs) (DR(-) T(regs)) and the highly differentiated …
Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells.
Summary Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper 2 (Th2) and Th17 cells. Herein, we report that IRF4 is also crucial for the development and function of an interleukin-9 (IL-9)-producing CD4 + T cell subset designated Th9. IRF4-deficient CD4 + T cells failed to develop into IL-9-producing Th9 cells, and IRF4-specific siRNA inhibited IL-9 production in wild-type CD4 + T cells. Chromatin-immunoprecipitation (ChIP) analyses revealed direct IRF4 binding to the Il9 promoter in Th9 cells. In a Th9-dependent asthma model, neutralization of IL-9 substantially ameliorated asthma symptoms. The relevance of these findings is emphasized by the fact that the ind…
DR(high+)CD45RA(-)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients.
Recent studies show that regulatory T cells (Tregs) play an essential role in tolerance induction after organ transplantation. In order to examine whether there are differences in the composition of the total CD4(+)CD127(low+/-)FoxP3(+)- Treg cell pool between stable transplant patients and patients with biopsy proven rejection (BPR), we compared the percentages and the functional activity of the different Treg cell subsets (DR(high+)CD45RA(-)-Tregs, DR(low+)CD45RA(-)-Tregs, DR(-)CD45RA(-)-Tregs, DR(-)CD45RA(+)-Tregs). All parameters were determined during the three different periods of time after transplantation (0-30 days, 31-1,000 days, >1,000 days). Among 156 transplant patients, 37 pat…