van den Dobbelsteen G P, Kroes H, van Rees E P
Department of Cell Biology and Immunology, Medical Faculty, Vrije Universiteit, Amsterdam, The Netherlands.
Scand J Immunol. 1995 Mar;41(3):273-80. doi: 10.1111/j.1365-3083.1995.tb03564.x.
The immune response to pneumococcal polysaccharide type 14 (PPS-14), induced by native PPS-14 was compared with the response induced by PPS-14 conjugated with CRM197 (PPS-14-CRM197). In our animal model, immunization with PPS-14-CRM197 gave a significant enhancement of anti-PPS-14 serum titres for IgM and IgG, but not for IgA. Also an increase in total number of anti-PPS-14 antibody-secreting cells was found. Using immunohistochemical techniques, a different distribution pattern of specific antibody-containing cells in spleen section after immunization with PPS-14-CRM197 was observed. Furthermore, a higher number of IFN-gamma producing cells was found after immunization with PPS-14-CRM197, as compared with immunization with PPS-14. This enhanced IFN-gamma production may be the cause for enhanced IgG response observed after immunization with PPS-14-CRM197. The specific immune response was less affected by splenectomy in animals immunized with PPS-14-CRM197 than with PPS-14. However, an age-related response to the native as well as the conjugated form of the PPS-14 was observed, since no effect of conjugation with CRM197 was seen in the onset of the immune response to PPS-14 in young animals. In conclusion, our results affirm the hypothesis that conjugation of polysaccharides changes the characteristics of the antigen towards a thymus-dependent antigen.
将天然14型肺炎球菌多糖(PPS - 14)诱导的免疫反应与CRM197偶联的14型肺炎球菌多糖(PPS - 14 - CRM197)诱导的免疫反应进行了比较。在我们的动物模型中,用PPS - 14 - CRM197免疫可显著提高抗PPS - 14血清中IgM和IgG的滴度,但对IgA无此作用。还发现抗PPS - 14抗体分泌细胞的总数有所增加。使用免疫组织化学技术,观察到用PPS - 14 - CRM197免疫后脾脏切片中含特异性抗体细胞的分布模式不同。此外,与用PPS - 14免疫相比,用PPS - 14 - CRM197免疫后发现产生干扰素γ的细胞数量更多。这种干扰素γ产生的增强可能是在用PPS - 14 - CRM197免疫后观察到的IgG反应增强的原因。在用PPS - 14 - CRM197免疫的动物中,特异性免疫反应受脾切除的影响比用PPS - 14免疫的动物小。然而,观察到对天然形式以及偶联形式的PPS - 14存在年龄相关反应,因为在幼龄动物对PPS - 14免疫反应的起始阶段未见到与CRM197偶联的效果。总之,我们的结果证实了多糖偶联会使抗原特性转变为胸腺依赖性抗原这一假说。