Marti W R, Schütz A, Oertli D, Zajac P, Harder F, Heberer M
Allgemeinchirurgische Klinik, Departement Chirurgie, Universität Basel, CH-4031 Basel.
Langenbecks Arch Chir Suppl Kongressbd. 1998;115(Suppl I):131-6.
A specific antigenic ligand and a costimulatory signal are required for optimal T cell activation. We constructed and tested recombinant Vaccinia viruses (recVV) expressing hB7-1 or hB7-2 as a gene expression vector system for delivery of costimulatory function in vitro. Upon infection with replication incompetent and non-cytopathic recVV B7, all human tumour cell lines tested expressed the recombinant molecules. Cell lines expressing recombinant B7 molecules provided effective costimulation for proliferation of resting CD4+ T helper cells in the presence of suboptimal PMA concentrations. The costimulatory effect could be blocked with soluble CTLA-4 proteins. RecVV B7-1 infected EBV transformed B-lymphocytes overexpressed the costimulatory molecules resulting in enhanced costimulation. The capacity of these cells to stimulate autologous CD4+ memory cells of VV immunocompetent donors was not impared by the recVV infection indicating an intact capacity for processing and presenting antigenic proteins in the context with MHC Class II molecules remained. RecVV encoding human B7 molecules therefore appear to be promising experimental and clinical tools to enhance immune responses.
最佳的T细胞激活需要特定的抗原配体和共刺激信号。我们构建并测试了表达hB7-1或hB7-2的重组痘苗病毒（recVV），将其作为一种基因表达载体系统，用于在体外传递共刺激功能。在用无复制能力且无细胞病变的recVV B7感染后，所有测试的人肿瘤细胞系均表达了重组分子。在亚最佳浓度佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）存在的情况下，表达重组B7分子的细胞系为静息CD4+辅助性T细胞的增殖提供了有效的共刺激。共刺激作用可被可溶性细胞毒性T淋巴细胞相关抗原4（CTLA-4）蛋白阻断。recVV B7-1感染的EB病毒转化的B淋巴细胞过度表达共刺激分子，导致共刺激增强。这些细胞刺激痘苗病毒免疫活性供体的自体CD4+记忆细胞的能力并未因recVV感染而受损，这表明其在与II类主要组织相容性复合体（MHC）分子结合的情况下加工和呈递抗原蛋白的能力保持完整。因此，编码人B7分子的recVV似乎是增强免疫反应的有前景的实验和临床工具。
