Anti-idiotypic antibodies to anti-HLA receptors induced by pregnancy.

Anti-idiotypic antibodies to anti-HLA receptors induced by pregnancy.
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妊娠诱导的抗 HLA 受体的抗独特型抗体。

DOI:
10.1073/pnas.80.3.830
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发表时间:
1983
影响因子:
11.1
通讯作者:
D. W. King
D. W. King
中科院分区:
综合性期刊1区
文献类型:
--
作者:
N. Suciu;E. Reed;C. Rohowsky;P. Kung;D. W. King

文献摘要

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我们之前已经证明,体外同种激活的淋巴母细胞具有刺激自体混合淋巴细胞反应的能力。这种反应本质上是抗独特型的,因为只有当被针对相同 HLA-DR 抗原同种激活的自体淋巴母细胞重新刺激时,如此引发的淋巴细胞才会表现出加速的记忆反应。基于这一观察,我们推测同种免疫人类受试者中 HLA 抗体的缺失可能是由于自身抗体的产生,该抗体与致敏淋巴细胞或抗 HLA 抗体或两者表达的抗 HLA 受体发生反应。这一假设已在目前的研究中得到证实,这些研究表明,经产妇女的血清与在 5 天混合淋巴细胞培养物中针对其丈夫(即表达免疫供体受体的淋巴细胞)的自体 T 淋巴细胞发生反应。 T 和 B 淋巴细胞表达的抗 HLA 受体似乎具有共同的血清学决定因素,因为与自体同种异体激活的淋巴母细胞结合的血清也能够抑制自体和同源血清的抗 HLA 活性。自身抗独特型抗体抑制自体混合淋巴细胞对自体同种异体激活的淋巴母细胞的反应,这种现象的体内相关性可能在于抗HLA抗体形成和同种异体移植免疫的自身抑制。由于在所有接受测试的经产妇女的血清中都发现了自身抗独特型抗体,因此对同种异体抗原无反应本身作为一种状态存在的假设不太可能。利用孕妇血清中的抗体被动转移抗受体(独特型)免疫可能为特异性抑制同种异体移植排斥反应提供有力的工具。
We have previously shown that lymphoblasts alloactivated in vitro acquire the capacity of stimulating the autologous mixed lymphocyte response. This response is anti-idiotypic in nature because lymphocytes so primed display accelerated memory responses only when restimulated by autologous lymphoblasts that have been alloactivated against the same HLA-DR antigen. Based on this observation we have postulated that the absence of HLA antibodies in alloimmunized human subjects may be due to the development of autoantibodies that react with the anti-HLA receptors expressed by primed lymphocytes or by anti-HLA antibodies or both. This hypothesis has been confirmed in the present investigations which show that sera from parous women react with autologous T lymphoblasts primed in 5-day mixed lymphocyte culture against their husband-i.e., with lymphoblasts expressing receptors for the immunizing donor. Anti-HLA receptors expressed by T and B lymphocytes seem to share serologic determinants because sera that bind to autologous alloactivated lymphoblasts are also capable of inhibiting the anti-HLA activity of autologous and homologous sera. Auto-anti-idiotypic antibodies inhibit the autologous mixed lymphocyte response to autologous alloactivated lymphoblasts, a phenomenon whose in vivo correlate may reside in autoinhibition of anti-HLA antibody formation and of allograft immunity. Because auto-anti-idiotypic antibodies were found in sera from all parous women tested, the hypothesis that nonresponsiveness to alloantigens exists as a state per se is not likely. The passive transfer of antireceptor (idiotype) immunity by use of antibodies from pregnant women's sera may provide a powerful tool for specific suppression of allograft rejection.