Funeshima-Fuji Naoko, Fujino Masayuki, Xie Lin, Kimura Hiromitsu, Takahara Shiro, Ezaki Taichi, Zhu Bao Ting, Li Xiao-Kang
Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
J Heart Lung Transplant. 2009 Feb;28(2):176-82. doi: 10.1016/j.healun.2008.11.914.
It has been suggested that pregnancy-related hormones play a critical role in mediating selective immune tolerance during pregnancy. An understanding of why a woman's body normally does not reject the fetus is highly relevant to the prevention of transplant rejection.
The hearts of female inbred F344 rats (RT-1(lvl)) were transplanted into naive Lewis (RT-1(l); nLewis) or pregnant (pLewis; Day 6, 12 and 18 of pregnancy) rats. The mean survival time (MST) of the cardiac allografts between the nLewis and pLewis rats was compared. We determined the rate of proliferation of the T cells isolated from nLewis and pLewis rats in response to concanavalin A (ConA), anti-CD3 and -CD28 antibody and alloantigen stimulation ex vivo. mRNA expression of several cytokines in these T cells was analyzed using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, the effect of estriol on the cardiac allograft was tested.
The pLewis rats with transplant on Day 12 of pregnancy had the most significantly prolonged F344 cardiac graft survival (MST 13.3 days) as compared with nLewis recipients (MST 8 days). pLewis T-cell proliferation was stimulated by alloantigen and antibody but ConA was reduced, whereas Th1/Th2 cytokine mRNA profiles in the T cells were similar for nLewis and pLewis rats. Likewise, estriol also significantly prolonged survival of cardiac allografts.
The results of this study demonstrate that pregnancy hormones not only appear to play a critical role in maternal acceptance of the fetus, but also have therapeutic potential for prolonging the survival of major histocompatibility complex (MHC)-compatible allografts during pregnancy.
有研究表明，妊娠相关激素在介导孕期选择性免疫耐受中起关键作用。了解女性身体为何通常不会排斥胎儿，对于预防移植排斥反应具有重要意义。
将雌性近交系F344大鼠（RT-1(lvl)）的心脏移植到未经免疫的Lewis大鼠（RT-1(l); nLewis）或怀孕大鼠（pLewis；孕期第6、12和18天）体内。比较nLewis和pLewis大鼠心脏同种异体移植的平均存活时间（MST）。我们测定了从nLewis和pLewis大鼠分离的T细胞在体外对刀豆蛋白A（ConA）、抗CD3和-CD28抗体以及同种异体抗原刺激的增殖率。使用定量逆转录聚合酶链反应（RT-PCR）分析这些T细胞中几种细胞因子的mRNA表达。此外，还测试了雌三醇对心脏同种异体移植的影响。
与nLewis受体（MST 8天）相比，在孕期第12天接受移植的pLewis大鼠，F344心脏移植物存活时间显著延长（MST 13.3天）。pLewis T细胞增殖受到同种异体抗原和抗体刺激，但ConA刺激减弱，而nLewis和pLewis大鼠T细胞中的Th1/Th2细胞因子mRNA谱相似。同样，雌三醇也显著延长了心脏同种异体移植的存活时间。
本研究结果表明，妊娠激素不仅似乎在母体对胎儿的接受中起关键作用，而且在孕期延长主要组织相容性复合体（MHC）匹配的同种异体移植存活时间方面具有治疗潜力。
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