Laboratory of Investigation in Dermatology and Immunodeficiencies, School of Medicine, University of São Paulo, São Paulo, Brazil.
J Clin Immunol. 2010 Mar;30(2):280-91. doi: 10.1007/s10875-009-9358-9. Epub 2010 Jan 19.
Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization.
The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice.
Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-gamma upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG.
Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases.
新生儿和成人的免疫反应存在多种差异。生命早期对 Th2 型反应或耐受的倾向使其容易受到感染和过敏敏化的影响。
本研究旨在评估含 CpG 寡脱氧核苷酸对卵清蛋白和布鲁氏菌属热带亚种提取物的新生儿和成人免疫接种的影响,并比较 CpG 对新生儿和成年小鼠 B 和 T 细胞的作用。
接受 CpG 的小鼠在新生儿和成年期的免疫球蛋白 E(IgE)抗体产生均减少,同时 IgG2a 抗体水平升高。我们观察到,接受早期 CpG 的小鼠的脾细胞在抗 CD3 刺激时产生更多的干扰素-γ。与新生儿相比,成年小鼠对 IgE 反应的负调控更为明显;此外,CpG 仅在成年小鼠中降低了过敏抗卵清蛋白 IgG1。此外,在 CpG 刺激下,成年 B 细胞中检测到 Toll 样受体 9 表达上调,但在新生儿 B 细胞中未检测到。与成年 B 细胞相比,新生儿 B 细胞在对 CpG 的反应中表现出更高的白细胞介素(IL)-10 表达和更低的 IL-6 水平。当我们分析体外 CD4+T 细胞的激活时,CpG 抑制了新生儿 T 细胞上 B7 分子的表达增加。
总之,我们验证了 CpG 对新生儿和成人变应原免疫接种的定性和定量影响的证据,这表明了解新生儿免疫系统的重要性,以制定预防过敏性疾病的免疫调节策略。