雌激素对大鼠脾脏单核细胞衍生的树突状细胞分化和功能的影响(英文)

Estrogen affects the differentiation and function of splenic monocyte-derived dendritic cells from normal rats

目的 :研究雌激素是否可通过影响树突状细胞 (DC)而调控实验性自身免疫性脑脊髓膜炎 (EAE)大鼠的免疫应答。方法 :在细胞因子和不同浓度的 17β 雌二醇存在下 ,从大鼠脾脏单核细胞培养DC ,用流式细胞仪检测DC表面分子 ,通过抗原提呈实验观察雌二醇处理的DC(E2 DC)抗原提呈能力是否改变。用含髓鞘碱性蛋白 (myelinbasicprotein ,MBP6 8- 86)的佐剂免疫大鼠 ,观察皮下或静脉注射E2 DC对EAE大鼠免疫应答是否有影响。结果 :17β 雌二醇可加速DC分化 ,特征性表现为CD11c、共刺激分子B7 2和CD40的上调 ,而抗原提呈能力未有改变。在DC和T细胞共培养的上清液中 ,IFN γ分泌下降而IL 10水平升高。给免疫 5d的EAE大鼠静脉注射E2 DC ,可激活淋巴结细胞的免疫应答 ,如提高细胞增殖能力和细胞因子产生 ,而脾脏产生MBP特异性抗体的细胞数量减少。结论 :雌激素能影响DC的分化和功能 ,导致Th2细胞因子产生 。

AIM: To explore the mechanism resulting in the preventive effect of estr ogen on experimental autoimmune encephalomyelitis (EAE), which is an animal mode l for multiple sclerosis (MS), and examine if estrogen can affect the immune res ponse in EAE at dendritic cell (DC) level. METHODS: Flow cytomet ry was used to reveal the surface marker expression. 3 H-thymi dine incorporation was applied to examine the cellular proliferation. Levels of anti-myelin basic protein (MBP) 68-86 antibody and cytokines were determin ed by enzyme-linked immunospot and ELISA, respectively. RESULTS : 17β-estradiol (E2) could dose-dependently accelerate the differentiatio n process of DCs by up-regulating CD11c, B7-2 and CD40 expressions, but exert no effect on its antigen presentation ability. MBP-specific T cells cocultured with E2-treated DCs (E2-DC) produced more IL-10 and less IFN-γ in the super natant than those without E2 pretreatment(ctr-DC). In contrast to ctr-DC, E2- DC, if injected i.v. into EAE rats on day 5 post immunization, could initiate an tigen nonspecific hyper-responsivity in T cells in terms of enhanced proliferat ion and cytokine secretion of mononuclear cells in LN, but suppressed antibody s ecretion from splenocytes. CONCLUSION: These results suggest tha t estrogen can affect the differentiation and function of DCs, which leads T cel ls switching to Th2 secretion.This may account partly for the protective effect of estrogen on EAE.