Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ T-regs in human second trimester pregnancy is induced by progesterone and 17 beta-estradiol
2009 (English)In: Journal of Reproductive Immunology(ISSN 0165-0378), vol 81, issue 2, 2009, Vol. 81, no 2, 160-161 p.Conference paper (Refereed)
CD4+CD25high regulatory T cells (Tregs) are implicated in maintenance of murine pregnancy. However, reports regarding circulating Treg frequencies in human pregnancy are inconsistent and the functionality and phenotype of these cells in pregnancy have not been clarified. The aim was to determine the frequency, phenotype and function of circulating Tregs in second trimester human pregnancy and the influence of progesterone and 17β-estradiol on Treg phenotype and frequency. Based on expression of Foxp3, CD127 and HLA-DR, as determined by multi-color flow cytometry, we defined a proper CD4dimCD25high Treg population and showed, in contrast to most previous reports, that this population was reduced in second trimester pregnancy. Unexpectedly, Foxp3 expression was decreased in the Treg, as well as in the CD4+ population. These changes could be replicated in an in vitro system resembling the pregnancy hormonal milieu, where 17β-estradiol, and in particular progesterone, induced, in line with the pregnancy situation, a reduction of CD4dimCD25highFoxp3+ cells in PBMC from non-pregnant women. By co-culturing FACS-sorted Tregs and autologous CD4+CD25- responder cells, we showed that Tregs from pregnant women still displayed the same suppressive capacity as non-pregnant women in terms of suppressing IL-2, TNF-α and IFN-γ secretion from responder cells while efficiently producing IL-4 and IL-10. Our findings support the view of hormones, particularly progesterone, as critical regulators of Tregs in pregnancy. Further, we suggest that in the light of the results of this study, early data on circulating Treg frequencies in pregnancy need re-evaluation.
Place, publisher, year, edition, pages
2009. Vol. 81, no 2, 160-161 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-21510DOI: 10.1016/j.jri.2009.06.225OAI: oai:DiVA.org:liu-21510DiVA: diva2:241461
Jenny Mjösberg, J Svensson, E Johansson, L Hellstrom, Rosaura Casas, Maria Jenmalm, R Boij, L Matthiesen, Jan-Ingvar Jönsson, Göran Berg and Jan Ernerudh, Systemic reduction of functionally suppressive CD4dimCD25highFoxp3+ Tregs in human second trimester pregnancy is induced by progesterone and 17 beta-estradiol, 2009, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (81), 2, 160-161.
Copyright: Elsevier Science B.V., Amsterdam.