Kinetics of the pregnancy-induced humoral and cellular immune response against the paternal HLA class I antigens of the child
Kinetics of the pregnancy-induced humoral and cellular immune response against the paternal HLA class I antigens of the child
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DOI：
10.1016/s0198-8859(02)00396-8
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发表时间：
2002-06-01
期刊：
影响因子：
2.7
通讯作者：
Claas, FHJ
中科院分区：
文献类型：
--
作者：
van Kampen, CA;Maarschalk, MFJVV;Claas, FHJ
怀孕可以启动母亲对孩子父亲人类白细胞抗原(HLA)的体液免疫反应。先前的研究已经报道，抗遗传的父系人类白细胞抗原抗体的形成与针对这些抗原的预置细胞毒性T淋巴细胞(CTL)的存在有关。最近，我们报道，即使抗体消失，启动的CTL也可以在怀孕后持续10年以上。在本研究中，我们研究了妊娠诱导的T细胞和B细胞免疫反应的动力学。我们分析了12例分娩时有父源抗FILA抗体的孕妇，从分娩时到产后2年，抗父源FILA抗原的CTLp频率。在缺乏和存在针对CD8的单抗的情况下，通过限制稀释分析来测试预置的CTL对这些CTLp频率的贡献。与单纯的CTL不同，启动的CTL对CD8抗体具有抵抗力。抗体的消失与针对父源抗原的CTLp数量的减少无关，而CTLp最初是针对父源抗原的。然而，在抗体消失的妇女中，发现预置的儿童错配特异性CTL减少，而在抗体持续存在的妇女中，预置CTL的数量在分娩后2年保持稳定。我们的数据表明T细胞和B细胞同种异体之间存在功能上的相关性。尽管动力学不是完全平行的，但在分娩后的头两年中，抗人类白细胞抗原抗体的消失与预置的儿童错配特异性CTL的减少有关。这些数据可能与既往有妊娠诱导的同种异体抗体的女性受体的移植有关。
Pregnancy can prime the maternal humoral immune response against paternal human leukocyte antigens (HLA) of the child. Previous studies have reported that formation of antibodies against inherited paternal HLA is associated with the presence of primed cytotoxic T lymphocytes (CTLs) specific for these antigens. Recently, we reported that primed CTLs can persist for more than 10 years after Pregnancy even if the antibodies have disappeared. In the present study we studied the kinetics of the Pregnancy induced immune response of the T-cell and B-cell compartment. In 12 women, who had specific antibodies against the paternal HLA antigens of the child (child mismatch) at the time of delivery, we analyzed the CTLp frequencies against the paternal FILA antigens from the time of delivery LIP to 2 years after. The contribution of primed CTLs to these CTLp frequencies was tested by limiting dilution analysis in the absence and presence of monoclonal antibodies specific for CD8. In contrast to naive CTLs, primed CTLs are resistant to CD8 antibodies. Disappearance of the antibodies was nor associated with a decrease of the number of CTLp directed against the paternal antigens, towards which the antibodies were originally directed. However, in women where the antibodies disappeared, a decrease of primed child mismatch specific CTLs was found, whereas in women where the antibodies Persist, the population of primed CTLs remained stable tip to 2 years after delivery. Our data suggest a functional correlation between the T-cell and B-cell allorepertoire. Although the kinetics do not run completely in parallel, disappearance of the anti-HLA antibodies in the first 2 years after delivery is related with a decrease of primed child mismatch specific CTLs. These data may be relevant for transplantation of female recipients with historical, pregnancy-induced HLA alloantibodies.