Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia.
Mol Immunol. 2009 Nov;47(1):141-6. doi: 10.1016/j.molimm.2009.01.012. Epub 2009 Feb 23.
Albino Oxford (AO) rats are resistant to induction of experimental autoimmune encephalomyelitis (EAE), in contrast to susceptible Dark Agouti (DA) rats. We have previously shown that draining lymph node cells (DLNC) obtained from immunized DA rats before the onset of the clinical disease produced more interferon (IFN)-gamma and interleukin (IL)-17 (signature cytokines of T(H)1 and T(H)17 responses, respectively) compared to DLNC from AO rats. In this study, we extend our analysis to entire induction phase of EAE with the emphasis on the T(H)1 and T(H)17-inducing cytokines. As a result, we show that throughout the inductive phase of the disease DLNC of DA rats, not only expressed higher levels of IFN-gamma and IL-17, but also of T(H)1-inducing cytokine-IL-12. As for T(H)17-inducing cytokines, DLNC of DA rats expressed more mRNA for p19, specific subunit of IL-23, but the expression of transforming growth factor (TGF)-beta in both strains was similar. Interestingly, the analysis of IL-6 expression revealed striking difference: while all DA DLNC were positive for IL-6 mRNA, cells from none of AO rats expressed detectable levels of mRNA for this cytokine. Taken together, our data suggest that the differential regulation of production of T(H)1 and T(H)17 cytokines, and IL-6 in particular, during the induction phase of disease could be responsible for the discrepancy in susceptibility to EAE between these two rat strains.
白化牛津（AO）大鼠对实验性自身免疫性脑脊髓炎（EAE）的诱导具有抗性，与易感的深色阿育王（DA）大鼠形成对比。我们之前已经表明，与来自 AO 大鼠的引流淋巴结细胞（DLNC）相比，在临床疾病发作之前从免疫的 DA 大鼠获得的 DLNC 产生了更多的干扰素（IFN）-γ和白细胞介素（IL）-17（分别为 TH1 和 TH17 反应的特征细胞因子）。在这项研究中，我们将我们的分析扩展到 EAE 的整个诱导阶段，重点是 TH1 和 TH17 诱导细胞因子。结果，我们表明在疾病的整个诱导阶段，DA 大鼠的 DLNC 不仅表达了更高水平的 IFN-γ和 IL-17，而且还表达了 TH1 诱导细胞因子-IL-12。至于 TH17 诱导细胞因子，DA 大鼠的 DLNC 表达了更多的 p19（IL-23 的特定亚基）mRNA，但两种菌株的转化生长因子（TGF）-β表达相似。有趣的是，IL-6 表达的分析显示出惊人的差异：虽然所有 DA DLNC 的 IL-6 mRNA 均为阳性，但来自 AO 大鼠的细胞均未表达可检测水平的这种细胞因子的 mRNA。总之，我们的数据表明，在疾病诱导阶段，TH1 和 TH17 细胞因子的产生，特别是 IL-6 的差异调节，可能是这两种大鼠品系对 EAE 易感性差异的原因。
