Wira Charles R, Rossoll Richard M
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756-0001, USA.
Immunology. 2003 Jul;109(3):398-406. doi: 10.1046/j.1365-2567.2003.01670.x.
We have previously shown that oestradiol treatment of ovariectomized rats for 3 days inhibits antigen presentation by uterine stromal cells at a time when oestradiol increases the numbers of antigen-presenting cells (APC) in the uterine stroma. In the present study, we found that oestradiol treatment for 1 day is sufficient to inhibit antigen presentation by stromal cells. To define the mechanism(s) of this inhibition, we examined the effect of cytokines and found that exogenous transforming growth factor-beta (TGF-beta) inhibits antigen presentation when stromal cells from saline- but not oestradiol-treated animals are incubated with ovalbumin (OVA)-specific T cells and OVA. In contrast, antigen presentation by uterine epithelial cells was not affected by TGF-beta. In other studies, the acute inhibitory effect of oestradiol (1 day) on stromal antigen presentation is fully reversed when anti-TGF-beta antibody is added to the culture media. When given for 3 days, oestradiol inhibition of antigen presentation is partially reversed by anti-TGF-beta antibody at a time when antibodies to tumour necrosis factor-alpha and interleukin-10 have no effect. To determine whether uterine epithelial cells produce TGF-beta, epithelial cells were grown to confluence on transwell inserts. Our findings indicate that uterine epithelial cells produce biologically active TGF-beta which is preferentially released basolaterally in the direction of underlying stromal cells. When oestradiol is given to ovariectomized rats 1 day before sacrifice, TGF-beta production by epithelial cells increases within 24 hr in culture, relative to saline controls. Taken together, these results suggest that oestradiol inhibition of stromal cell antigen presentation is mediated through the stimulatory effect of oestradiol on TGF-beta production by epithelial cells.
我们之前已经表明，对去卵巢大鼠进行3天的雌二醇处理，在雌二醇增加子宫基质中抗原呈递细胞（APC）数量的同时，会抑制子宫基质细胞的抗原呈递。在本研究中，我们发现1天的雌二醇处理就足以抑制基质细胞的抗原呈递。为了确定这种抑制的机制，我们检测了细胞因子的作用，发现当用卵清蛋白（OVA）特异性T细胞和OVA培养来自生理盐水处理而非雌二醇处理动物的基质细胞时，外源性转化生长因子-β（TGF-β）会抑制抗原呈递。相比之下，子宫上皮细胞的抗原呈递不受TGF-β的影响。在其他研究中，当向培养基中添加抗TGF-β抗体时，雌二醇（1天）对基质抗原呈递的急性抑制作用会完全逆转。当给予3天时，在肿瘤坏死因子-α和白细胞介素-10抗体无效的情况下，抗TGF-β抗体可部分逆转雌二醇对抗原呈递的抑制作用。为了确定子宫上皮细胞是否产生TGF-β，将上皮细胞在Transwell小室中培养至汇合。我们的研究结果表明，子宫上皮细胞产生具有生物活性的TGF-β，其优先从基底外侧释放到下方的基质细胞方向。当在处死前1天给去卵巢大鼠注射雌二醇时，相对于生理盐水对照组，培养24小时内上皮细胞产生的TGF-β增加。综上所述，这些结果表明，雌二醇对基质细胞抗原呈递的抑制作用是通过雌二醇对上皮细胞产生TGF-β的刺激作用介导的。
