Shojaeian Jaleh, Moazzeni Seyed Mohammad, Nikoo Shohreh, Bozorgmehr Mahmood, Nikougoftar Mahin, Zarnani Amir Hassan
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
J Reprod Immunol. 2007 Aug;75(1):23-31. doi: 10.1016/j.jri.2007.02.006. Epub 2007 Apr 16.
In normal pregnancy, the maternal immune system is directed towards tolerance or suppression in order to prevent rejection of the semi-allogenic fetus. Antigen-presenting cells, especially dendritic cells (DCs), are key cells in initiation and regulation of immune responses. The presence of potent immunostimulatory DCs in the decidual tissue of pregnancy has been demonstrated. The aim of this study was to determine how allostimulatory activity of DCs could be affected during pregnancy. DCs were isolated from spleen of pregnant or non-pregnant Balb/c mice and co-cultured with allogenic T lymphocytes prepared from brachial lymph nodes of C57BL/6 mice. Some cultures of non-pregnant female DCs were treated by 2.5% serum obtained from pregnant mice at early, middle or late gestational periods, and were used in the same mixed lymphocyte reaction (MLR) settings. Cell proliferation was measured by 3H-thymidine incorporation, and cytokine production measured in supernatants of MLR cultures using ELISA. The effect of pregnant mouse serum on expression of DC surface markers was evaluated by flow cytometry. No significant difference was found between stimulatory potential of splenic DCs from pregnant and non-pregnant mice in induction of allogenic T cell proliferative response. Moreover, serum of early or late pregnancy did not have any effect on DC function in comparison with non-pregnant mouse serum, while mid-pregnancy serum significantly inhibited allostimulatory activity of DCs. IFNgamma production in co-culture of DCs treated with pregnant mouse serum was significantly lower than that of the control group; however, no significant difference in IL-10 production was observed. Treatment of DCs with pregnant mouse serum did not influence the percentage of cells expressing MHC-II, CD86, CD8alpha or CD11b. However, a marked reduction of the mean fluorescence intensity of MHC-II was observed. Collectively, our results concerning the diminished capacity of DCs to induce production of Th1 cytokines and allogenic T cell proliferation after treatment with pregnant mouse serum reveal a new way of immunologic tolerance against the semi-allogenic fetus.
在正常妊娠中，母体免疫系统倾向于产生耐受性或抑制作用，以防止对半同种异体胎儿的排斥。抗原呈递细胞，尤其是树突状细胞（DCs），是免疫反应启动和调节的关键细胞。妊娠蜕膜组织中存在强效免疫刺激DCs已得到证实。本研究的目的是确定妊娠期间DCs的同种异体刺激活性如何受到影响。从怀孕或未怀孕的Balb/c小鼠脾脏中分离出DCs，并与从C57BL/6小鼠臂淋巴结制备的同种异体T淋巴细胞共培养。一些未怀孕雌性DCs的培养物用妊娠早期、中期或晚期怀孕小鼠的2.5%血清处理，并用于相同的混合淋巴细胞反应（MLR）设置。通过3H-胸腺嘧啶核苷掺入法测量细胞增殖，并使用酶联免疫吸附测定法（ELISA）测量MLR培养上清液中的细胞因子产生。通过流式细胞术评估怀孕小鼠血清对DC表面标志物表达的影响。在诱导同种异体T细胞增殖反应方面，怀孕和未怀孕小鼠脾脏DCs的刺激潜力之间未发现显著差异。此外，与未怀孕小鼠血清相比，妊娠早期或晚期血清对DC功能没有任何影响，而妊娠中期血清显著抑制DCs的同种异体刺激活性。用怀孕小鼠血清处理的DCs共培养物中IFNγ的产生明显低于对照组；然而，在IL-10产生方面未观察到显著差异。用怀孕小鼠血清处理DCs不影响表达MHC-II、CD86、CD8α或CD11b的细胞百分比。然而，观察到MHC-II的平均荧光强度显著降低。总体而言，我们关于用怀孕小鼠血清处理后DCs诱导Th1细胞因子产生和同种异体T细胞增殖能力降低的结果揭示了一种针对半同种异体胎儿的免疫耐受新方式。
