Lachapelle M H, Miron P, Hemmings R, Roy D C
Institut de Médecine de la Reproduction de Montréal, Department of Obstetrics-Gynecology, Quebec, Canada.
J Immunol. 1996 May 15;156(10):4027-34.
Several lines of evidence indicate that immunologic effectors, particularly suppressor T cells and NK cells, may play a role in the pathogenesis of idiopathic repetitive abortions. To investigate the involvement of these immune cell populations, we determined the immunophenotypic characteristics of endometrial leukocytes from nonpregnant recurrent aborters. Habitual aborters with a negative investigation underwent an endometrial biopsy during their secretory phase and were followed prospectively to assess clinical outcome. Endometrial leukocytes were evaluated by two-color flow cytometric analysis. The percentage of endometrial CD8+ T lymphocytes was significantly decreased in recurrent aborters, and their CD4:CD8 ratio was increased. In contrast, the proportion of B lymphocytes (CD20+) was strikingly increased in these patients' endometria. The proportion of NK cells was identical in recurrent aborters and normal controls, but the CD16-CD56 bright NK cell subset, which is predominant in normal decidua and endometrium, was significantly decreased in favor of an important contingent of CD16+CD56 dim NK cells in all habitual aborters. Repetitive aborters who had normal CD8+ and CD20+ cell numbers and a normal CD4:CD8 ratio subsequently underwent successful pregnancies, while patients with continuing abortions presented lymphoid populations observed in the habitual aborters group. In conclusion, endometrial lymphocytes of recurrent spontaneous aborters harbor a distinct immunophenotypic profile that antedates implantation and suggests that endometrial immunologic conditions are intrinsically altered in recurrent aborters. Also, the prognostic impact of CD8 and CD20 expression supports their predominant role in the development of fetal tolerance. Finally, a role for NK cells in the abortion process is suggested by their altered subsets in all repetitive aborters.
多项证据表明，免疫效应细胞，尤其是抑制性T细胞和自然杀伤（NK）细胞，可能在特发性复发性流产的发病机制中起作用。为了研究这些免疫细胞群体的参与情况，我们确定了非妊娠复发性流产者子宫内膜白细胞的免疫表型特征。对检查结果为阴性的习惯性流产者在其分泌期进行子宫内膜活检，并进行前瞻性随访以评估临床结局。通过双色流式细胞术分析评估子宫内膜白细胞。复发性流产者子宫内膜CD8 + T淋巴细胞百分比显著降低，其CD4：CD8比值升高。相反，这些患者子宫内膜中B淋巴细胞（CD20 +）的比例显著增加。复发性流产者和正常对照者的NK细胞比例相同，但在所有习惯性流产者中，正常蜕膜和子宫内膜中占主导的CD16 - CD56bright NK细胞亚群显著减少，有利于CD16 + CD56dim NK细胞的重要群体。CD8 +和CD20 +细胞数量正常且CD4：CD8比值正常的复发性流产者随后成功妊娠，而持续流产的患者呈现出习惯性流产者组中观察到的淋巴细胞群体。总之，复发性自然流产者的子宫内膜淋巴细胞具有独特的免疫表型特征，早于着床，提示复发性流产者子宫内膜免疫状况发生了内在改变。此外，CD8和CD20表达的预后影响支持它们在胎儿耐受性发展中的主要作用。最后，所有复发性流产者中NK细胞亚群的改变提示其在流产过程中起作用。
