First Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
J Reprod Immunol. 2011 Sep;91(1-2):56-63. doi: 10.1016/j.jri.2011.03.012. Epub 2011 Jul 18.
Preeclampsia (PE) is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive arms of the immune system. Granulysin is a cytolytic and pro-inflammatory molecule expressed by activated human cytotoxic T lymphocytes and natural killer (NK) cells. Recent data show that serum granulysin levels are elevated in preeclampsia. The purpose of this study was to determine whether the proportion of peripheral blood cytotoxic T lymphocytes and NK cells that express intracellular granulysin is altered in PE. Twenty-two preeclamptic patients and 29 healthy pregnant women were involved in this case-control study. Intracellular granulysin expression of lymphocytes was determined with flow cytometric examination. In healthy pregnant women, the majority of NK cells and a small fraction of cytotoxic T cells expressed granulysin in their cytoplasma (median (25-75 percentile): 53.5 (45.6-68.0)% and 13.8 (8.5-23.1)%, respectively). In PE, the percentage of granulysin-positive cytotoxic T lymphocytes was markedly increased, while the proportion of granulysin-producing NK cells was unchanged as compared to healthy pregnant women (for cytotoxic T cells: 34.1 (19.3-45.6)%, p<0.001; for NK cells: 57.2 (42.9-74.9)%, p>0.05). Maternal age of healthy pregnant women showed a significant inverse correlation with the frequency of granulysin-expressing NK cells (Spearman R=-0.44, p<0.05), while their BMI correlated positively with the proportions of granulysin-positive cytotoxic T cells and NK cells (Spearman R=0.43, p<0.05 for both). In conclusion, the majority of circulating NK cells but only a small population of cytotoxic T cells shows intracellular granulysin expression in normal pregnancy. In preeclampsia, the proportion of granulysin-producing cytotoxic T cells in the peripheral blood is markedly increased, which might contribute to the development of the pro-inflammatory Th1-type immune responses characteristics of the maternal syndrome of the disease.
子痫前期 (PE) 是一种严重的妊娠并发症，其特征是母体全身性炎症反应过度，固有免疫和适应性免疫均被激活。颗粒酶是一种细胞溶解和促炎分子，由激活的人细胞毒性 T 淋巴细胞和自然杀伤 (NK) 细胞表达。最近的数据表明，子痫前期患者血清颗粒酶水平升高。本研究旨在确定外周血细胞毒性 T 淋巴细胞和 NK 细胞中表达细胞内颗粒酶的比例是否在 PE 中发生改变。本病例对照研究纳入了 22 例子痫前期患者和 29 例健康孕妇。通过流式细胞术检测淋巴细胞内颗粒酶的表达。在健康孕妇中，大多数 NK 细胞和一小部分细胞毒性 T 细胞在细胞质中表达颗粒酶（中位数（25-75 百分位）：53.5（45.6-68.0）%和 13.8（8.5-23.1）%）。在 PE 中，与健康孕妇相比，颗粒酶阳性细胞毒性 T 淋巴细胞的百分比明显增加，而产生颗粒酶的 NK 细胞的比例不变（对于细胞毒性 T 细胞：34.1（19.3-45.6）%，p<0.001；对于 NK 细胞：57.2（42.9-74.9）%，p>0.05）。健康孕妇的年龄与 NK 细胞表达颗粒酶的频率呈显著负相关（Spearman R=-0.44，p<0.05），而 BMI 与颗粒酶阳性细胞毒性 T 细胞和 NK 细胞的比例呈正相关（Spearman R=0.43，p<0.05）。总之，在正常妊娠中，大多数循环 NK 细胞但只有一小部分细胞毒性 T 细胞表达细胞内颗粒酶。在子痫前期中，外周血中产生颗粒酶的细胞毒性 T 细胞的比例明显增加，这可能有助于疾病母体综合征特征的促炎 Th1 型免疫反应的发展。
