Bai Xue-Feng, Liu Jinqing, May Kenneth F, Guo Yong, Zheng Pan, Liu Yang
Department of Pathology and the Comprehensive Cancer Center, Ohio State University Medical Center, Columbus 43210, USA.
Blood. 2002 Apr 15;99(8):2880-9. doi: 10.1182/blood.v99.8.2880.
Costimulatory molecules B7-1 and B7-2 (hereby collectively called B7) interact with CD28 and CTLA4 on T cells and promote antitumor immunity. The function of B7-CTLA4 interaction in antitumor CTL response remains controversial. Here we used CD28(-/-) and CD28(+/-) or CD28(+/+) transgenic mice that express the T-cell receptor specific for an unmutated tumor antigen, P1A, and for tumor cells expressing a CTLA4-specific B7 mutant to evaluate the function of CD28-B7 and CTLA4-B7 interactions in induction and effector phases of antitumor immunity. We report that B7-CD28 and B7-CTLA4 interactions promote tumor rejection. However, this is achieved by distinct mechanisms. B7-CD28 interaction enhances T-cell clonal expansion, though a role for this interaction in the effector phase cannot be ruled out. In contrast, B7-CTLA4 interaction enhances the CTL-mediated destruction of tumors, but not T-cell clonal expansion.
共刺激分子B7-1和B7-2（以下统称为B7）与T细胞上的CD28和CTLA4相互作用，促进抗肿瘤免疫。B7-CTLA4相互作用在抗肿瘤CTL反应中的功能仍存在争议。在此，我们使用表达针对未突变肿瘤抗原P1A的T细胞受体以及表达CTLA4特异性B7突变体的肿瘤细胞的CD28(-/-)和CD28(+/-)或CD28(+/+)转基因小鼠，来评估CD28-B7和CTLA4-B7相互作用在抗肿瘤免疫的诱导和效应阶段的功能。我们报告B7-CD28和B7-CTLA4相互作用促进肿瘤排斥。然而，这是通过不同机制实现的。B7-CD28相互作用增强T细胞克隆扩增，尽管不能排除这种相互作用在效应阶段的作用。相比之下，B7-CTLA4相互作用增强CTL介导的肿瘤破坏，但不增强T细胞克隆扩增。
