Fetal alloantigen is responsible for the expansion of the CD4+CD25+ regulatory T cell pool during pregnancy
Fetal alloantigen is responsible for the expansion of the CD4+CD25+ regulatory T cell pool during pregnancy
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DOI：
10.1016/j.jri.2007.06.052
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发表时间：
2007-10-01
影响因子：
3.4
通讯作者：
Liu, Yi
中科院分区：
文献类型：
--
作者：
Zhao, Jing-xian;Zeng, Yao-ying;Liu, Yi
越来越多的证据表明，CD4(+)CD25(+)调节性T细胞(Treg)参与妊娠期间母体对胎儿耐受性的发展；然而，人们对控制Tregs活动的因素知之甚少。本研究通过分析同基因妊娠小鼠(BALB/c x BALB/c)、异基因妊娠小鼠(BALB/c x C57)、去卵巢小鼠和孕妇的CD4(+)CD25(+) Tregs，探讨胎儿同种异体抗原和妊娠相关激素对Tregs活性的影响。结果表明，异体妊娠小鼠中 CD4(+)CD25(+) Tregs 的频率比同基因妊娠小鼠增加更多，这导致与同基因妊娠小鼠相比，同种异体妊娠小鼠对父本抗原的同种反应性降低。增加的 Tregs 最有可能是在外周淋巴组织中诱导的，而不是在胸腺中发育的。同种异体交配的小鼠和人类的 Treg 频率具有相似的动态变化，在妊娠早期显着增加，从妊娠中期开始逐渐减少，直至足月时恢复到非妊娠水平。人类引产似乎与 CD4(+)CD25(高) Tregs 的减少和 CD4(+)CD25(低) T 细胞的增加有关。无论是雌激素或孕激素单独使用，还是它们的组合，都没有显示出对卵巢切除小鼠中 Tregs 频率的影响。这些结果表明胎儿同种异体抗原是妊娠期间Treg细胞增加的原因，Treg细胞数量的增加对于同种异体胎儿逃避母体免疫攻击具有重要意义。 (c) 2007 Elsevier Ireland Ltd. 保留所有权利。
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/c x BALB/c), allogeneically pregnant mice (BALB/c x C57), 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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.