Ng Siu Chui, Gilman-Sachs Alice, Thaker Poonam, Beaman Kenneth D, Beer Alan E, Kwak-Kim Joanne
Department of Microbiology and Immunology, Finch University of Health Sciences/The Chicago Medical School, IL 60064, USA.
Am J Reprod Immunol. 2002 Aug;48(2):77-86. doi: 10.1034/j.1600-0897.2002.01105.x.
We aimed to investigate absolute counts of intracellular T helper 1 (Th1) and Th2 cytokine expressing T-cell subpopulations in women with three or more recurrent spontaneous abortions (RSA), multiple implantation failures after in-vitro fertilization and embryo transfer (IVF/ET) (three or more) or during normal pregnancy.
Absolute cell counts and percentages of CD3+, CD3+/CD4+, and CD3+/CD8+ T-cell populations expressing intracellular cytokines [interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4 and IL-10] was studied by four-color flow cytometry in 15 RSA and 13 implantation failure patients. Eighteen fertile non-pregnant and 47 normal pregnant women were also compared with regard to intracellular cytokine expression.
Interleukin-10 producing CD3+/CD8+ T-cell counts were significantly lower in women with RSA (P < 0.05) and implantation failures (P < 0.05), and TNF-alpha producing CD3+/CD4+ T-cell counts were higher in women with RSA (P < 0.05) and implantation failures (P < 0.005) than those of non-pregnant fertile controls. During normal pregnancies, first trimester IL-4 expressing CD3+, CD3+/CD4+ T-cell counts (P < 0.05) and IFN-gamma expressing CD3+ T-cell counts (P < 0.05) were significantly higher than those of third trimester (P < 0.05). First trimester TNF-alpha expressing CD3+/CD8+ T-cell counts were significantly higher than those of second and third trimester women (P < 0.05). However, there are no differences in cytokine expression between non-pregnant and first trimester pregnant women.
Absolute counts of IFN-gamma, IL-4, and TNF-alpha expressing T cells decrease with the progress of gestation (third trimester) during normal pregnancies. In women with implantation failures, absolute cell counts of TNF-alpha expressing CD3+/ 4- cells reflects the presence of dominant Th1 immune response. A significantly increased Th1 cytokine expression may be the underlying immune etiology for reproductive failures.
我们旨在调查复发性自然流产（RSA）三次及以上、体外受精与胚胎移植（IVF/ET）后多次着床失败（三次及以上）或正常妊娠期间女性体内表达细胞内辅助性T细胞1（Th1）和辅助性T细胞2（Th2）细胞因子的T细胞亚群的绝对计数。
采用四色流式细胞术研究了15例RSA患者和13例着床失败患者中表达细胞内细胞因子[干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-4和IL-10]的CD3⁺、CD3⁺/CD4⁺和CD3⁺/CD8⁺T细胞群体的绝对细胞计数和百分比。还比较了18例未孕有生育能力的女性和47例正常妊娠女性的细胞内细胞因子表达情况。
RSA患者（P<0.05）和着床失败患者（P<0.05）中产生IL-10的CD3⁺/CD8⁺T细胞计数显著降低，RSA患者（P<0.05）和着床失败患者（P<0.005）中产生TNF-α的CD3⁺/CD4⁺T细胞计数高于未孕有生育能力的对照者。在正常妊娠期间，孕早期表达IL-4的CD3⁺、CD3⁺/CD4⁺T细胞计数（P<0.05）和表达IFN-γ的CD3⁺T细胞计数（P<0.05）显著高于孕晚期（P<0.05）。孕早期表达TNF-α的CD3⁺/CD8⁺T细胞计数显著高于孕中期和孕晚期女性（P<0.05）。然而，未孕女性和孕早期女性之间的细胞因子表达没有差异。
在正常妊娠期间，表达IFN-γ、IL-4和TNF-α的T细胞绝对计数随着妊娠进展（孕晚期）而降低。在着床失败的女性中，表达TNF-α的CD3⁺/CD4⁺细胞的绝对细胞计数反映了占主导地位的Th1免疫反应的存在。Th1细胞因子表达显著增加可能是生殖失败的潜在免疫病因。
