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 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(+)-naive Treg pool and thus retains the maintenance of pregnancy.
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
Miriam I
MI
Wagner
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
Charlotte
C
Mai
Institute of Immunology, University of Mainz, Mainz, Germany.
Edgar
E
Schmitt
Department of Dermatology, University of Heidelberg, Heidelberg, Germany.
Karsten
K
Mahnke
Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
Stefan
S
Meuer
Department of Medicine V (Hematology), University of Heidelberg, Heidelberg, Germany.
Volker
V
Eckstein
Department of Medicine V (Hematology), University of Heidelberg, Heidelberg, Germany.
Anthony D
AD
Ho
Department of Medicine I (Nephrology), University of Heidelberg, Heidelberg, Germany.
Matthias
M
Schaier
Department of Medicine I (Nephrology), University of Heidelberg, Heidelberg, Germany.
Martin
M
Zeier
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
Julia
J
Spratte
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
Herbert
H
Fluhr
Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany.
Andrea
A
Steinborn
D000293:Adolescent; D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008875:Middle Aged; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D055815:Young Adult
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D017493:Leukocyte Common Antigens