Oertli D, Marti W R, Norton J A, Tsung K
Department of Surgery, University Hospital of Basel, Switzerland.
J Gen Virol. 1996 Dec;77 ( Pt 12):3121-5. doi: 10.1099/0022-1317-77-12-3121.
Using a series of new insertion/expression vectors, we constructed a set of recombinant vaccinia viruses (recVV) encoding the murine T cell costimulatory molecules mB7-1 or mB7-2, or both together in the same construct. On infection with replication incompetent and non-cytopathic recVV, several tumour cell lines expressed the respective molecules and bound to CTLA-4. The highest binding capacity was found when both mB7 molecules were co-expressed. Mouse B16.F10 melanoma cells expressing mB7-1 or mB7-2 provided effective costimulation for proliferation of resting CD4+ T cells in the presence of concanavalin A and plate-bound anti-T cell receptor antibodies, respectively. If mB7-1 and mB7-2 were delivered together on the same cell, the proliferative response of CD4+ T cells increased further. The costimulatory effect could be blocked with CTLA-4, the soluble ligand for B7 molecules. The possibility of engineering tumour cells using recVV holds implications for the future design of vaccination strategies.
我们使用一系列新的插入/表达载体，构建了一组重组痘苗病毒（recVV），它们在同一构建体中编码小鼠T细胞共刺激分子mB7-1或mB7-2，或二者共同编码。用无复制能力且无细胞病变的recVV感染后，几种肿瘤细胞系表达了相应分子并与CTLA-4结合。当两个mB7分子共表达时，发现结合能力最强。分别表达mB7-1或mB7-2的小鼠B16.F10黑色素瘤细胞，在伴刀豆球蛋白A和板结合抗T细胞受体抗体存在的情况下，分别为静息CD4+ T细胞的增殖提供了有效的共刺激。如果mB7-1和mB7-2在同一细胞上共同递送，CD4+ T细胞的增殖反应会进一步增强。共刺激作用可以被B7分子的可溶性配体CTLA-4阻断。利用recVV改造肿瘤细胞的可能性，对未来疫苗接种策略的设计具有重要意义。
