Geldhof A B, Raes G, Bakkus M, Devos S, Thielemans K, De Baetselier P
Laboratory of Cellular Immunology, Flemish Institute for Biotechnology, Free University of Brussels, Sint Genesius Rode.
Cancer Res. 1995 Jul 1;55(13):2730-3.
The interaction between B7-1 and CD28 provides costimulatory signals not only for T cells but also for natural killer (NK) cells. Highly metastatic mouse T lymphoma cells (BW-Li) can escape from NK cell-mediated killing by expressing H-2Dk molecules that negatively regulate NK lytic activity. We have analyzed whether B7-1:CD28 overrules the MHC class I-mediated inactivation of NK cells by transfecting BW-Li with the gene coding for B7-1. Expression of B7-1 rendered BW-Li cells sensitive toward NK cells. The experimental metastatic capacity of the B7-1 transfectants was drastically reduced in both syngeneic AKR and SCID mice but could be restored in SCID-bg mice. These results provide direct evidence that B7-1 expression leads to NK-mediated elimination of metastasizing, NK-resistant tumor cells.
B7-1与CD28之间的相互作用不仅为T细胞提供共刺激信号，也为自然杀伤（NK）细胞提供共刺激信号。具有高度转移性的小鼠T淋巴瘤细胞（BW-Li）可通过表达负向调节NK细胞溶解活性的H-2Dk分子，逃避NK细胞介导的杀伤作用。我们通过用编码B7-1的基因转染BW-Li细胞，分析了B7-1:CD28是否能克服MHC I类分子介导的NK细胞失活。B7-1的表达使BW-Li细胞对NK细胞敏感。在同基因AKR小鼠和SCID小鼠中，B7-1转染子的实验转移能力均大幅降低，但在SCID-bg小鼠中可恢复。这些结果提供了直接证据，表明B7-1的表达导致NK细胞介导的对转移性、NK抗性肿瘤细胞的清除。
