Koszinowski U H, Reddehase M J, Keil G M, Volkmer H, Jonjic S, Messerle M, del Val M, Mutter W, Münch K, Bühler B
Dept. of Microbiology, Bundesforschungsanstalt für Viruskrankheiten der Tiere, Tübingen, F.R.G.
Immunol Lett. 1987 Dec;16(3-4):185-92. doi: 10.1016/0165-2478(87)90146-5.
The infection of the mouse with murine cytomegalovirus (MCMV) served as a model system to understand the biology of human CMV infection. The contribution of cytolytic T lymphocytes (CTL) to the recovery from infection was studied. Protection against lethal MCMV disease could be conferred on immunodepleted hosts by adoptive transfer of lymphocytes. The antiviral effect was mediated by specifically sensitized T lymphocytes of the CD8+ subset. These cells limited viral spread, prevented tissue destruction by viral cytopathic effects, and protected from lethal disease. Transferred cells have protective therapeutic function even when the virus has already colonized host tissues. CD8+ cells do not require the contribution of CD4+ cells for in vivo function. Selective expression of immediate-early (IE) phase genes in target cells allowed the detection of the immunodominant IE antigen recognized by CTL. The major IE gene ieI encodes a non-structural viral phosphoprotein, pp89, which resides in the nucleus of infected cells where it acts as transcriptional regulator. Expression of gene ieI is under temporal control, and membrane presentation of the protein domain detected by CTL is down-regulated by MCMV early-phase products. A recombinant vaccinia virus expressing gene ieI induced immunity that protected mice against a subsequent challenge with a lethal dose of MCMV. The protective effect was entirely mediated by CD8+ T lymphocytes. Thus, an experimental vaccine expressing a single nonstructural herpesvirus protein can induce a protective cellular immune response.
用鼠巨细胞病毒（MCMV）感染小鼠作为一个模型系统，以了解人类巨细胞病毒感染的生物学特性。研究了细胞毒性T淋巴细胞（CTL）在感染恢复过程中的作用。通过淋巴细胞的过继转移，可以使免疫缺陷宿主获得针对致死性MCMV疾病的保护。抗病毒效应由CD8 +亚群的特异性致敏T淋巴细胞介导。这些细胞限制病毒传播，防止病毒细胞病变效应导致的组织破坏，并保护机体免受致死性疾病侵害。即使病毒已经在宿主组织中定植，转移的细胞仍具有保护性治疗功能。CD8 +细胞在体内发挥功能不需要CD4 +细胞的参与。靶细胞中立即早期（IE）阶段基因的选择性表达使得能够检测到CTL识别的免疫显性IE抗原。主要的IE基因ieI编码一种非结构性病毒磷蛋白pp89，它存在于受感染细胞的细胞核中，在那里作为转录调节因子发挥作用。基因ieI的表达受时间控制，CTL检测到的蛋白结构域的膜呈现被MCMV早期产物下调。表达基因ieI的重组痘苗病毒诱导的免疫可保护小鼠免受致死剂量MCMV的后续攻击。保护作用完全由CD8 + T淋巴细胞介导。因此，表达单一非结构性疱疹病毒蛋白的实验性疫苗可诱导保护性细胞免疫反应。
