Olafsdottir T A, Hannesdottir S G, Giudice G D, Trannoy E, Jonsdottir I
Department of Immunology, Landspitali-University Hospital, and Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Scand J Immunol. 2007 Oct;66(4):426-34. doi: 10.1111/j.1365-3083.2007.01970.x.
The immature state of the immune system of neonates makes them vulnerable to infectious agents, including Streptococcus pneumoniae. The aim of our study was to analyse and compare the effects of Escherichia coli heat-labile enterototoxin (LT)-K63 and CpG2006 on cells and key molecules of the neonatal immune system, using a previously established immunization model with pneumococcal polysaccharide of serotype 1 conjugated to tetanus toxoid (TT) (Pnc1-TT). The cellular response was evaluated by measuring cytokine secretion and proliferation upon in vitro stimulation with TT, the protein moiety of Pnc1-TT, and antibody (Ab) to both the polysaccharide (PS) and protein parts of the vaccine were measured by enzyme-linked immunosorbent assay (ELISA). Antigen (Ag)-presenting and co-stimulatory capacity of neonatal B-cells was evaluated by staining for major histocompatibility complex (MHC)II, CD80, CD86 and CD40. The results showed that both LT-K63 and CpG2006 significantly enhanced the neonatal Ab response to Pnc1-TT. Spleen cells from mice receiving LT-K63 showed enhanced proliferation and interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 secretion upon TT stimulation, whereas cells from mice receiving CpG2006 could only enhance IL-10 secretion. LT-K63 and to a lesser extent CpG2006 enhanced the capacity of B-cells to up-regulate the expression of co-stimulatory and activation markers compared with those of mice receiving Pnc1-TT alone. Thus, we conclude that LT-K63 markedly improves T-cell activation whereas the direct adjuvant effect of CpG2006 on neonatal B-cells may partly compensate for lower T-cell help resulting in enhanced neonatal Ab responses to both the TT and PS parts of the vaccine by both adjuvants.
新生儿免疫系统的不成熟状态使他们易受包括肺炎链球菌在内的感染因子的侵害。我们研究的目的是使用先前建立的1型肺炎球菌多糖与破伤风类毒素（TT）偶联（Pnc1-TT）的免疫模型，分析和比较大肠杆菌不耐热肠毒素（LT）-K63和CpG2006对新生儿免疫系统细胞和关键分子的影响。通过测量用TT（Pnc1-TT的蛋白质部分）体外刺激后的细胞因子分泌和增殖来评估细胞反应，并用酶联免疫吸附测定（ELISA）测量针对疫苗多糖（PS）和蛋白质部分的抗体（Ab）。通过对主要组织相容性复合体（MHC）II、CD80、CD86和CD40进行染色来评估新生儿B细胞的抗原（Ag）呈递和共刺激能力。结果表明，LT-K63和CpG2006均显著增强了新生儿对Pnc1-TT的抗体反应。接受LT-K63的小鼠的脾细胞在TT刺激后显示出增强的增殖以及干扰素（IFN）-γ、白细胞介素（IL）-4、IL-5和IL-10分泌，而接受CpG2006的小鼠的细胞仅增强了IL-10分泌。与仅接受Pnc1-TT的小鼠相比，LT-K63以及在较小程度上CpG2006增强了B细胞上调共刺激和激活标志物表达的能力。因此，我们得出结论，LT-K63显著改善T细胞活化，而CpG2006对新生儿B细胞的直接佐剂作用可能部分补偿较低的T细胞辅助，导致两种佐剂均增强新生儿对疫苗TT和PS部分的抗体反应。
