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Wiley, Immunology & Cell Biology, 10(93), p. 858-867

DOI: 10.1038/icb.2015.51

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The role of recent thymic emigrant-regulatory T cell (RTE-Treg) differentiation during pregnancy

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This paper is available in a repository.

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Abstract

During pregnancy, regulatory T cells (Tregs) play a key role in maternal immune tolerance to the semi-allogeneic fetus. Our previous results showed that the naïve CD45RA(+)-Treg pool is functionally improved in pregnant women compared to 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, while that of the CD45RA(+)CD31(-)-mature naive (MN)-Tregs did not change and that of the CD45RA(-)CD31(-)-memory Tregs increased complementary. Thereby, the ratio of RTE-/MN-Tregs decreased from 1.0 to 0.7 leading to a significant increase in the suppressive activity of the naive CD45RA(+)-Treg pool. This effect was confirmed by re-assembling separated RTE- and MN-Tregs from non-pregnant women in the ratio of pregnant women. The suppressive activity of both separated naive Treg subsets was equally high in non-pregnant and pregnant women, but considerably reduced in preeclampsia patients, who showed significantly increased percentages of CD45RA(-)CD31(+)-memory Tregs, but decreased percentages of RTE- and MN-Tregs. Our results suggest a reduced thymic output of RTE-Tregs during pregnancy, which causes a decrease in the ratio of RTE-/MN-Tregs and thus an increase in the differentiation of RTE-Tregs towards CD45RA(-)CD31(-)-memory Tregs. Presumably, this differentiation of RTE-Tregs, which was impaired in preeclampsia patients, ensures the improved suppressive activity of the CD45RA(+)-naïve Treg pool and thus retains the maintenance of pregnancy.Immunology and Cell Biology accepted article preview online, 27 April 2015. doi:10.1038/icb.2015.51.