Hasenkrug K J, Brooks D M, Nishio J, Chesebro B
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA.
J Virol. 1996 Jan;70(1):368-72. doi: 10.1128/JVI.70.1.368-372.1996.
Friend murine leukemia virus is a retrovirus complex that induces rapid erythroleukemia and immunosuppression in susceptible strains of adult mice. Using this model, we directly examined the T-cell subsets required for a protective retrovirus vaccine. Paradoxically, recovery in mice immunized with a chimeric envelope containing only T-helper (TH) and B-cell epitopes was dependent on CD8+ T cells as well as CD4+ T cells despite the fact that the vaccine contained no CD8+ cytolytic T-lymphocyte (CTL) epitopes. However, the requirement for CD8+ T cells was overcome by inclusion of additional TH and B-cell epitopes in the immunizing protein. These additional epitopes primed for more rapid production of virus-neutralizing antibody which appeared to limit virus spread sufficiently to protect even in the absence of CD8+ T cells. Inclusion of an immunodominant CTL epitope in the vaccine was not sufficient to overcome dependence on CD4+ T cells. These data suggest that TH priming is more critical for retrovirus immunity than CTL priming.
Friend小鼠白血病病毒是一种逆转录病毒复合体，可在成年小鼠的易感品系中诱发快速的红白血病和免疫抑制。利用该模型，我们直接检测了保护性逆转录病毒疫苗所需的T细胞亚群。矛盾的是，用仅包含T辅助（TH）和B细胞表位的嵌合包膜免疫的小鼠的恢复依赖于CD8 + T细胞以及CD4 + T细胞，尽管该疫苗不含CD8 + 细胞溶解性T淋巴细胞（CTL）表位。然而，通过在免疫蛋白中加入额外的TH和B细胞表位，对CD8 + T细胞的需求得以克服。这些额外的表位引发了更快速的病毒中和抗体产生，这似乎足以限制病毒传播，即使在没有CD8 + T细胞的情况下也能起到保护作用。在疫苗中加入免疫显性CTL表位不足以克服对CD4 + T细胞的依赖性。这些数据表明，TH引发对于逆转录病毒免疫比CTL引发更为关键。
