Laboratory of Immunology, Institute of Pediatrics, Obstetrics and Gynecology, Academy of Medical Sciences of Ukraine, Kiev, Ukraine.
Am J Reprod Immunol. 2010 Jul 1;64(1):58-67. doi: 10.1111/j.1600-0897.2010.00825.x. Epub 2010 Mar 17.
The aim of this study was to evaluate the role of elevated natural killer cytotoxicity (NKc) in women with multiple implantation failures (IF) in vitro fertilization-embryo transfer (IVF-ET) cycles.
Seventy-nine antiphospholipid antibodies-negative women with IF including 33 women with elevated NKc were selected for investigation. K-562 cell line was used to evaluate NKc. Lymphocyte subsets, intracellular cytokines [interferon (IFN)-gamma, interleukin (IL)-4, tumour necrosis factor, IL-10], expression of activating markers [CD69, human leukocyte antigen (HLA)-DR], CD8, KIR (CD158a), CD95, and chemokine receptors (CXCR3, CCR4) were estimated by flow cytometry.
In women with IF, levels of NKc were higher than in IVF successful women. IF was associated with higher expression of CD8, CD158a, and HLA-DR in NK cells, activating markers in T lymphocytes, and lower levels of CCR4+ and IL-4+ T lymphocyte subsets. Predictive value of single elevated NKc for IVF success was 0.85, but addition of two other abnormal parameters resulted in its decrease to <0.39.
Elevated NKc is negative factor, though not critical for implantation in IVF cycles. Immune mechanism of IVF failure includes not only elevated NKc but also some other factors, such as elevated expression of CD8 and CD158a on NK cells, T lymphocyte activation, and diminished T helper 2 parameters.
本研究旨在评估体外受精-胚胎移植(IVF-ET)周期中多次着床失败(IF)的女性中自然杀伤细胞细胞毒性(NKc)升高的作用。
选择 79 名抗磷脂抗体阴性的 IF 患者,包括 33 名 NKc 升高的患者进行研究。使用 K-562 细胞系评估 NKc。通过流式细胞术估计淋巴细胞亚群、细胞内细胞因子[干扰素(IFN)-γ、白细胞介素(IL)-4、肿瘤坏死因子、IL-10]、激活标志物[CD69、人类白细胞抗原(HLA)-DR]、CD8、KIR(CD158a)、CD95 和趋化因子受体(CXCR3、CCR4)的表达。
IF 患者的 NKc 水平高于 IVF 成功患者。IF 与 NK 细胞中 CD8、CD158a 和 HLA-DR 的表达升高、T 淋巴细胞中激活标志物的表达升高以及 CCR4+和 IL-4+T 淋巴细胞亚群水平降低有关。单个 NKc 升高对 IVF 成功的预测值为 0.85,但增加另外两个异常参数会使其降低至<0.39。
虽然 NKc 升高不是 IVF 周期中着床的关键因素,但它是一个负面因素。IVF 失败的免疫机制不仅包括 NKc 升高,还包括其他一些因素,如 NK 细胞上 CD8 和 CD158a 的表达升高、T 淋巴细胞活化以及辅助性 T 细胞 2 参数减少。