Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan.
J Reprod Immunol. 2010 Jun;85(2):121-9. doi: 10.1016/j.jri.2010.02.006. Epub 2010 May 2.
Maternal T cells acquire a transient state of tolerance specific for paternal alloantigens during pregnancy. CD4(+)CD25(+) regulatory T (Treg) cells play a central role in induction and maintenance of tolerance. We have studied the role of Treg cells for the maintenance of allogeneic pregnancy during the implantation period, early pregnancy period and late pregnancy period. We performed depletion of Treg cells using treatment with anti-CD25 monoclonal antibody (mAb) in allogeneic or syngeneic pregnant mice. BALB/c or C57BL/6 female mice were mated with BALB/c or C57BL/6 male mice, and anti-CD25 mAb was injected intraperitoneally on day 2.5 post-coitum (pc), or days 4.5 and 7.5 pc, or days 10.5 and 13.5 pc. Administration of 0.5mg of anti-CD25 mAb induced depletion of CD4(+)CD25(+)Foxp3(+) Treg cells in both allogeneic and syngeneic pregnancy. The extent of depletion of CD4(+)CD25(+) Treg cells in spleen cells was 82.7%. This mAb treatment on day 2.5 pc of pregnancy induced implantation failure in allogeneic pregnant mice, but not in syngeneic pregnant mice. In addition, anti-CD25 mAb treatment on days 4.5 and 7.5 pc significantly increased resorption rates in allogeneic pregnant mice, but not in syngeneic pregnant mice. Interestingly, anti-CD25mAb treatment on days 10.5 and 13.5 pc reduced Treg cell numbers, but this treatment did not induce any abnormal pregnancy parameters such as intrauterine growth restriction, hypertension, or proteinuria. These findings suggest that CD4(+)CD25(+)Foxp3(+) Treg cells are important to mediate maternal tolerance to the allogeneic fetus in the implantation phase and early stage of pregnancy, but Treg cells might not be necessary for maintenance of the late stage of allogeneic pregnancy.
母体 T 细胞在怀孕期间获得针对父系同种异体抗原的短暂耐受状态。CD4(+)CD25(+)调节性 T (Treg) 细胞在诱导和维持耐受中发挥核心作用。我们研究了 Treg 细胞在胚胎着床期、早孕期和晚孕期维持同种异体妊娠中的作用。我们使用抗 CD25 单克隆抗体 (mAb) 处理来耗尽同种异体或同基因妊娠小鼠中的 Treg 细胞。BALB/c 或 C57BL/6 雌性小鼠与 BALB/c 或 C57BL/6 雄性小鼠交配，在受精后第 2.5 天（pc）、第 4.5 和 7.5 pc 天或第 10.5 和 13.5 pc 天经腹腔注射抗 CD25 mAb。给予 0.5mg 抗 CD25 mAb 可诱导同种异体和同基因妊娠中 CD4(+)CD25(+)Foxp3(+)Treg 细胞的耗竭。脾细胞中 CD4(+)CD25(+)Treg 细胞的耗竭程度为 82.7%。这种 mAb 处理在妊娠第 2.5 pc 天诱导同种异体妊娠小鼠着床失败，但在同基因妊娠小鼠中没有。此外，抗 CD25 mAb 处理在第 4.5 和 7.5 pc 天显著增加了同种异体妊娠小鼠的吸收率，但在同基因妊娠小鼠中没有。有趣的是，抗 CD25 mAb 处理在第 10.5 和 13.5 pc 天减少了 Treg 细胞数量，但这种处理不会引起宫内生长受限、高血压或蛋白尿等任何异常妊娠参数。这些发现表明，CD4(+)CD25(+)Foxp3(+)Treg 细胞对于介导母体对同种异体胎儿在着床期和妊娠早期的耐受至关重要，但 Treg 细胞对于维持同种异体妊娠的晚期可能不是必需的。
