Nashar T O, Webb H M, Eaglestone S, Williams N A, Hirst T R
Research School of Biosciences, University of Kent, Canterbury, Great Britain.
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):226-30. doi: 10.1073/pnas.93.1.226.
The importance of receptor binding in the potent immunogenicity of Escherichia coli heat-labile enterotoxin B subunit (EtxB) was tested by comparing its immunogical properties with those of a receptor binding mutant, EtxB(G33D). Subcutaneous immunization of EtxB(G33D) resulted in 160-fold reduction in antibody titer compared with wild-type EtxB, whereas its oral delivery failed to provoke any detectable secretory or serum anti-B subunit responses. Moreover, the two proteins induced strikingly different effects on lymphocyte cultures in vitro. EtxB, in comparison with EtxB(G33D), caused an increase in the proportion of B cells, many of which were activated (CD25+); the complete depletion of CD8+ T cells; an increase in the activation of CD4+ T cells; and an increase in interleukin 2 and a decrease in interferon gamma. These data indicate that EtxB exerts profound effects on immune cells, suggesting that its potent immunogenicity is dependent not only on efficient receptor-mediated uptake, but also on direct receptor-mediated immunomodulation of lymphocyte subsets.
通过将大肠杆菌热不稳定肠毒素B亚基（EtxB）的免疫学特性与其受体结合突变体EtxB（G33D）的特性进行比较，测试了受体结合在EtxB强大免疫原性中的重要性。与野生型EtxB相比，皮下注射EtxB（G33D）导致抗体效价降低了160倍，而口服给药未能引发任何可检测到的分泌性或血清抗B亚基反应。此外，这两种蛋白质在体外对淋巴细胞培养物产生了截然不同的影响。与EtxB（G33D）相比，EtxB导致B细胞比例增加，其中许多B细胞被激活（CD25+）；CD8+T细胞完全耗竭；CD4+T细胞的激活增加；白细胞介素2增加，干扰素γ减少。这些数据表明，EtxB对免疫细胞具有深远影响，表明其强大的免疫原性不仅依赖于有效的受体介导摄取，还依赖于对淋巴细胞亚群的直接受体介导免疫调节。
