Kwon S S, Kim N, Yoo T J
Division of Allergy and Immunology, Department of Medicine, University of Tennessee School of Medicine, 956 Court Ave., Memphis, TN 38163, USA.
Allergy. 2001 Aug;56(8):741-8. doi: 10.1034/j.1398-9995.2001.056008741.x.
Immunization with naked plasmid DNA leads to strong and persistent cell-mediated and humoral immune response to plasmid encoded antigen. Vaccination of DNA encoded whole allergen has been tried, but little information is currently available on the efficacy of DNA encoding T-cell epitopes in allergic disease. The purpose of this study was to determine whether the vaccination of naked plasmid DNA encoding only T-cell epitopes suppresses the allergic reaction as effectively as naked DNA encoding whole segments of allergen.
We immunized mice with a mixed naked plasmid DNA encoding the five classes of murine T-cell epitopes on Der p 1 and Der p 2 three times at weekly intervals via an intramuscular injection of BALB/c mice. Control mice were injected with the pcDNA 3.1 blank vector. After 3 weeks, the mice were actively sensitized twice and allowed to inhale the Der p extracts intranasally six times at weekly intervals.
The vaccinated mice showed a significant attenuated induction of Der p-specific immunoglobulin E synthesis compared to controls. In terms of the Der p-specific IgG2a antibody response, the vaccinated mice showed more prominent responses than the control mice group. In addition, analysis of the cytokine profile after Der p stimulation of the lymph-node cells revealed that the level of the mRNA expression of the interferon-gamma gene was higher in the vaccinated mice than in the controls. Histologic studies showed a much reduced infiltration of inflammatory cells in lung tissue of the gene-vaccinated mice in comparison with the controls.
These results suggest that vaccination with DNA encoding T-cell epitopes effectively inhibits allergen-induced IgE synthesis and reduces cell infiltration in lung tissue. Thus, gene therapy using T-cell epitope-encoding DNA presents an ideal way of combating allergic disease in the future.
用裸质粒DNA进行免疫可引发针对质粒编码抗原的强烈且持久的细胞介导免疫和体液免疫反应。人们已尝试对DNA编码的全过敏原进行疫苗接种，但目前关于DNA编码T细胞表位在过敏性疾病中的疗效的信息较少。本研究的目的是确定仅编码T细胞表位的裸质粒DNA疫苗接种是否能像编码过敏原全长片段的裸DNA一样有效地抑制过敏反应。
我们通过肌肉注射BALB/c小鼠，每周一次，共三次，用编码Der p 1和Der p 2上五类小鼠T细胞表位的混合裸质粒DNA免疫小鼠。对照小鼠注射pcDNA 3.1空载体。3周后，对小鼠进行两次主动致敏，并让其每周一次经鼻吸入Der p提取物，共六次。
与对照组相比，接种疫苗的小鼠Der p特异性免疫球蛋白E合成的诱导明显减弱。就Der p特异性IgG2a抗体反应而言，接种疫苗的小鼠比对照组小鼠表现出更显著的反应。此外，对Der p刺激后的淋巴结细胞的细胞因子谱分析显示，接种疫苗的小鼠中干扰素-γ基因的mRNA表达水平高于对照组。组织学研究表明，与对照组相比，基因疫苗接种小鼠肺组织中炎性细胞的浸润明显减少。
这些结果表明，用编码T细胞表位的DNA进行疫苗接种可有效抑制过敏原诱导的IgE合成，并减少肺组织中的细胞浸润。因此，使用编码T细胞表位的DNA进行基因治疗是未来对抗过敏性疾病的理想方法。
