Fetal alloantigen is responsible for the expansion of the CD4(+)CD25(+) regulatory T cell pool during pregnancy.
Increasing evidence suggests that CD4(+)CD25(+) regulatory T cells (Tregs) participate in the development of maternal tolerance to the fetus during pregnancy; however, the factors controlling the activities of Tregs are poorly understood. In the present study, CD4(+)CD25(+) Tregs were analyzed in syngeneically pregnant mice (BALB/cxBALB/c), allogeneically pregnant mice (BALB/cxC57), ovariectomized mice and pregnant women to investigate the influences of fetal alloantigens and pregnancy-related hormones on the activities of Tregs. It was demonstrated that the frequencies of CD4(+)CD25(+) Tregs increase more in allogeneically than in syngeneically pregnant mice, which contributes to a lowered alloreactivity against paternal antigens in allogeneically compared with syngeneically pregnant mice. The increased Tregs are most likely to be induced in peripheral lymphoid tissues, rather than develop in thymus. Allogeneically mated mice and humans share similar dynamic changes in Treg frequencies, markedly increasing during early pregnancy and progressively decreasing from mid-gestation onwards to return to non-pregnant levels at term. Induction of labor in humans appears to be associated with a decrease of CD4(+)CD25(high) Tregs and increase of CD4(+)CD25(low) T cells. Neither estrogen or progesterone alone, nor their combination, shows an impact on the frequencies of Tregs in ovariectomized mice. These results suggest that fetal alloantigen is responsible for the increase of Tregs during pregnancy, and the expansion of the Treg population is of importance for the allogeneic fetus to evade immune attack from the mother.
Zhao
Jing-Xian
JX
Institute for Tissue Transplantation and Immunology, Jinan University, Guangzhou, China. zhaojingxian@gmail.com
Zeng
Yao-Ying
YY
Liu
Yi
Y
D000293:Adolescent; D000328:Adult; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011247:Pregnancy / Q000276:immunology*; D011374:Progesterone / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens; D011374:Progesterone; D004958:Estradiol