Hill J A, Polgar K, Anderson D J
Fearing Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
JAMA. 1995 Jun 28;273(24):1933-6.
To test the hypothesis that peripheral blood mononuclear cells in women with unexplained recurrent abortion (URA) produce T-helper 1 (TH1)-type cytokines in response to trophoblast antigens.
Cohort study.
Medical center.
A total of 244 women with URA, 13 reproductively normal parous control women, and 10 men.
Supernatants from trophoblast-activated peripheral blood mononuclear cells from all participants were tested for toxic effects on mouse embryos and by enzyme-linked immunosorbent assay (ELISA) for interferon gamma (IFN-gamma). Supernatants from 20 URA patients with embryotoxic activity and IFN-gamma, 13 reproductively normal parous women, and 10 men were further tested by ELISA for other TH1-type cytokines (interleukin-2 [IL-2], tumor necrosis factor-beta [TNF-beta]), TH2-type cytokines (IL-4, IL-10), and TNF-alpha.
Embryotoxic activity was detected in supernatants from 160 of 244 URA patients and in none of the controls. Interferon gamma was detected in supernatants from 125 of 244 URA patients and was significantly associated with embryotoxicity (121 of 160 supernatants with embryotoxicity vs four of 84 supernatants without embryotoxicity [P < .001]). Of 20 supernatants from patients chosen for further study, all were positive for TNF-alpha, 17 for TNF-beta, two for IL-10, and one for IL-4. No cytokines were detected in supernatants from unstimulated or red blood cell membrane-activated cells of women with URA. In contrast, trophoblast-activated lymphocyte supernatants from reproductively normal women and men neither were embryotoxic nor contained TH1-type cytokines, but most contained the TH2-type cytokine IL-10. Three supernatants from reproductively normal women also contained IL-4.
Whereas TH1-type immunity to trophoblast is associated with URA and may play a role in reproductive failure, TH2-type immunity may be a natural response to trophoblast contributing to successful pregnancy.
检验不明原因复发性流产（URA）女性外周血单个核细胞在受到滋养层抗原刺激后产生辅助性T细胞1（TH1）型细胞因子这一假说。
队列研究。
医疗中心。
共有244例URA女性、13例生殖功能正常的经产妇对照女性以及10名男性。
检测所有参与者经滋养层激活的外周血单个核细胞的上清液对小鼠胚胎的毒性作用，并通过酶联免疫吸附测定（ELISA）检测γ干扰素（IFN-γ）。对20例具有胚胎毒性活性且产生IFN-γ的URA患者、13例生殖功能正常的经产妇以及10名男性的上清液，进一步通过ELISA检测其他TH1型细胞因子（白细胞介素-2 [IL-2]、肿瘤坏死因子-β [TNF-β]）、TH2型细胞因子（IL-4、IL-10）以及TNF-α。
在244例URA患者中，160例患者的上清液检测到胚胎毒性活性，而对照组均未检测到。在244例URA患者中，125例患者的上清液检测到γ干扰素，且与胚胎毒性显著相关（160例具有胚胎毒性活性的上清液中有121例，84例无胚胎毒性活性的上清液中有4例[P <.001]）。在选取进行进一步研究的20例患者的上清液中，所有样本TNF-α均呈阳性，17例TNF-β呈阳性，2例IL-10呈阳性，1例IL-4呈阳性。URA女性未受刺激或经红细胞膜激活的细胞上清液中未检测到细胞因子。相比之下，生殖功能正常的女性和男性经滋养层激活的淋巴细胞上清液既无胚胎毒性，也不含有TH1型细胞因子，但大多数含有TH2型细胞因子IL-10。3例生殖功能正常女性的上清液也含有IL-4。
虽然对滋养层的TH1型免疫与URA相关，且可能在生殖失败中起作用，但TH2型免疫可能是对滋养层的一种自然反应，有助于成功妊娠。
