BALB/c小鼠作为单纯疱疹病毒1型感染模型的免疫学分析

摘要

To investigate the immunological responses of BALB/c mice to herpes simplex virus type 1 (HSV-1) infection, the following factors were followed: strains, infect routes and mouse ages, the dendritic cells (DCs) and HSV-1 specific T cell rate and function in peripheral blood mononuclear cells (PBMCs), serum neutralizing antibody titer, and CD8+ T cell infiltration in nervous tissues in HSV-1-infected BALB/c mice.The results showed that 3-week-and 6-week-old BALB/c mice challenged with HSV-1 Mckrae and 17+ strains through corneal and nasal routes led to an increased rate of DCs in PBMCs, and conferred DC capacity to stimulate HSV-1 specific T cells in vivo.At 35 d post infection, low level interferon γ (IFN-γ)+ T cells and no interleukin 4 (IL4)+ T cells could be detected in PBMCs, and low level neutralizing antibody was present or absent in serum.Ninety days after BALB/c mice challenged with HSV-1 through subcutaneous and foot pad injection, CD8+ T cells could be detected in mouse trigeminal ganglia in different groups.However, HSV-1 specific IFN-γ+ T cell and IL4+ T cell rates showed divergence between different virus strains and mouse ages.Foot pad injection of BALB/c mice with HSV-1 could elicit higher neutralizing antibody titer compared with subcutaneous injection.This research demonstrated that, infection of different age BALB/c mice with different HSV-1 strains through different routes can stimulate comparable DC maturation and antigen presentation.%在单纯疱疹病毒1型(herpes simplex virus type 1,HSV-1)小鼠感染及其相关研究中,临床病理和免疫学指标对其分析具有重要技术意义.本研究观察了HSV-1在不同条件下感染BALB/c小鼠后的多个免疫学指标,包括外周血单核细胞(peripheral blood mononuclear cell,PBMC)群体中树突细胞比例及功能、血清中和抗体水平、PBMC中HSV-1抗原特异性T细胞水平,以及潜伏感染期小鼠神经组织中CD8+ T细胞浸润情况.结果显示,HSV-1毒株Mckrae、17+以角膜及滴鼻途径感染3周龄及6周龄BALB/c小鼠后,小鼠PBMC中树突细胞数量增加,并显示出刺激病毒抗原特异性T细胞增殖的能力.病毒感染后35 d,小鼠PBMC中未检测到白细胞介素4(interleukin 4,IL-4)+抗原特异性T细胞,但能检测到低水平的γ干扰素(interferon γ,IFN-γ)+抗原特异性T细胞;小鼠血清中未检测到或仅能检测到低水平的中和抗体.HSV-1以皮下及足垫注射途径感染BALB/c小鼠90 d后,足垫感染途径较皮下感染诱导出更高水平的血清中和抗体,PBMC中可检测到IL-4+及IFN-γ+抗原特异性T细胞,但不同毒株及小鼠周龄之间出现T细胞反应程度差异.组织病理学结果表明,各组小鼠三叉神经组织中均有CD8+ T细胞浸润.这些结果提示,不同HSV-1毒株以不同途径感染不同周龄BALB/c小鼠后,均可刺激树突细胞成熟及呈递病毒抗原,但血清中和抗体及PBMC中病毒抗原特异性T细胞水平在不同毒株、感染途径及小鼠周龄之间有差异.