Bromander A K, Kjerrulf M, Holmgren J, Lycke N
Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
Scand J Immunol. 1993 Apr;37(4):452-8. doi: 10.1111/j.1365-3083.1993.tb03318.x.
In the present study we show that cholera toxin (CT) strongly potentiates antigen presentation by intestinal epithelial cells, probably by enhancing co-stimulation. This was demonstrated in an allogeneic system using cells from the IEC-17 rat epithelial cell line as antigen presenting cells (APC). These cells were induced by optimal concentrations of IFN-gamma to express good amounts of Ia antigen and cultured for 24-48 h in the presence or absence of CT. Thereafter the cells were thoroughly washed and added to cultures containing MHC-incompatible spleen cells as responder cells. Epithelial cells exposed to CT demonstrated greatly enhanced ability to trigger allogen-specific T-cell proliferation as compared with IEC-17 cells treated with IFN-gamma alone. The mechanism for the enhanced APC function was investigated by analysing CT-treated IEC-17 cells for increased class II MHC antigen expression or enhanced production of cytokines with known co-stimulatory function. We found no significant increase in class II MHC antigen expression. By contrast, CT strongly promoted, in a dose-dependent fashion, the production of both IL-1 and IL-6 cytokines by IEC-17 cells as compared with untreated epithelial cells. This effect of CT was specific and not due to contaminating endotoxin because excess amounts of soluble toxin receptor, ganglioside GM1, added to the IEC-17 cultures completely abrogated the cytokine response to CT. These results together with our previous findings of enhanced antigen presentation by macrophages stimulated by CT suggest that the potent adjuvant function of CT for induction of mucosal immune responses might be attributed to an enhanced co-stimulating ability of several putative APC in the mucosal immune system: macrophages, B cells and epithelial cells.
在本研究中，我们发现霍乱毒素（CT）可通过增强共刺激作用，有力地增强肠上皮细胞的抗原呈递能力。这一现象在一个异基因系统中得到了证实，该系统使用来自IEC-17大鼠上皮细胞系的细胞作为抗原呈递细胞（APC）。这些细胞用最佳浓度的γ干扰素诱导，以表达适量的Ia抗原，并在有或无CT的情况下培养24 - 48小时。之后，将细胞彻底洗涤，并加入含有MHC不相容脾细胞作为反应细胞的培养物中。与仅用γ干扰素处理的IEC-17细胞相比，暴露于CT的上皮细胞触发同种异体特异性T细胞增殖的能力大大增强。通过分析经CT处理的IEC-17细胞中II类MHC抗原表达的增加或具有已知共刺激功能的细胞因子产生的增强，对APC功能增强的机制进行了研究。我们发现II类MHC抗原表达没有显著增加。相比之下，与未处理的上皮细胞相比，CT以剂量依赖的方式强烈促进IEC-17细胞产生IL-1和IL-6两种细胞因子。CT的这种作用是特异性的，并非由于内毒素污染，因为向IEC-17培养物中添加过量的可溶性毒素受体神经节苷脂GM1完全消除了对CT的细胞因子反应。这些结果连同我们之前关于CT刺激巨噬细胞增强抗原呈递的发现表明，CT对诱导黏膜免疫反应的强大佐剂功能可能归因于黏膜免疫系统中几种假定的APC（巨噬细胞、B细胞和上皮细胞）共刺激能力的增强。
