Stites D P, Bugbee S, Siiteri P K
J Reprod Immunol. 1983 Jul;5(4):215-28. doi: 10.1016/0165-0378(83)90237-1.
Progesterone and glucocorticoids share important anti-inflammatory and immunosuppressive properties. Both hormones have potent anti-proliferative effects in MLR, mitogen activation and cytotoxic T-cell generation. We investigated the cellular target of this in vitro anti-proliferative activity by comparing the effects of progesterone and cortisol on lymphocyte-monocyte interaction in concanavalin (Con A) induced human T-cell activation. Three different in vitro systems for assessing monocyte dependent T-cell activation by Con A were used: (1) limiting concentration of monocyte, (2) preincubation of isolated populations of monocytes and T cells with steroids and (3) role of steroid on action of Interleukin-1 (IL-1) activity. Monocytes separated from human peripheral blood leukocytes by flotation gradients and adherence to plastic were cultured at concentrations of 0.5-10% with constant numbers of isolated autologous T cells. Inhibition of Con A activation in cortisol (0.1-10 micrograms/ml) treated cultures was inversely proportional to percent monocytes, whereas in progesterone (2.0-20 micrograms/ml) treated cultures, inhibition was independent of monocyte concentration. Separated monocytes preincubated with progesterone and cultured with fresh T cells supported normal (108 +/- 7% control) levels of activation, but progesterone treated T cells and fresh monocytes responded at about 60% control levels. Similar experiments with cortisol (1 or 10 micrograms/ml) revealed significantly reduced responses when either cell population was preincubated with steroid. IL-1 induced by LPS stimulation of monocytes was blocked in its ability to stimulate Con A induced T cell proliferation with either steroid present during the assay of IL-1. These data provide additional support for local immunosuppression by steroids in the placenta during pregnancy. They suggest that progesterone selectively blocks T cell activation by a direct effect on T cells, whereas cortisol interferes with both monocytes and T cells.
孕酮和糖皮质激素具有重要的抗炎和免疫抑制特性。这两种激素在混合淋巴细胞反应（MLR）、有丝分裂原激活及细胞毒性T细胞生成方面均具有强大的抗增殖作用。我们通过比较孕酮和皮质醇对伴刀豆球蛋白（Con A）诱导的人T细胞活化过程中淋巴细胞 - 单核细胞相互作用的影响，研究了这种体外抗增殖活性的细胞靶点。使用了三种不同的体外系统来评估Con A诱导的单核细胞依赖性T细胞活化：（1）单核细胞的极限浓度；（2）分离的单核细胞和T细胞群体与类固醇进行预孵育；（3）类固醇对白细胞介素 - 1（IL - 1）活性作用的影响。通过浮选梯度和贴壁法从人外周血白细胞中分离出的单核细胞，以0.5 - 10%的浓度与恒定数量的自体分离T细胞进行培养。在皮质醇（0.1 - 10微克/毫升）处理的培养物中，Con A活化的抑制与单核细胞百分比呈反比，而在孕酮（2.0 - 20微克/毫升）处理的培养物中，抑制与单核细胞浓度无关。用孕酮预孵育分离的单核细胞并与新鲜T细胞一起培养，可支持正常（108±7%对照）的活化水平，但经孕酮处理的T细胞和新鲜单核细胞的反应约为对照水平的60%。用皮质醇（1或10微克/毫升）进行的类似实验表明，当任何一种细胞群体与类固醇预孵育时，反应均显著降低。在IL - 1测定期间，若存在任何一种类固醇，LPS刺激单核细胞诱导产生的IL - 1刺激Con A诱导的T细胞增殖的能力均被阻断。这些数据为孕期胎盘类固醇的局部免疫抑制提供了额外支持。它们表明，孕酮通过直接作用于T细胞选择性地阻断T细胞活化，而皮质醇则干扰单核细胞和T细胞。
