Faas S J, Pan S, Pinkert C A, Brinster R L, Knowles B B
J Exp Med. 1987 Feb 1;165(2):417-27. doi: 10.1084/jem.165.2.417.
The ability to mount an immune response to simian virus 40 (SV40) T antigen was evaluated using mice from two distinct SV40 transgenic lines derived from injection of the same gene construct. Our studies demonstrate functional immune tolerance to SV40 T antigen in a SV40 transgenic line that consistently develops tumors of the choroid plexus by 7 mo of age. Antibodies to SV40 T antigen are undetectable in the serum of these animals; furthermore, mice from this line are unable to generate SV40-specific CTL after primary or secondary immunization with the virus, although they mount a normal CTL response to vaccinia virus when appropriately immunized. In contrast, we find that mice from a second transgenic line of low tumor incidence can mount a humoral response to SV40 T antigen, and upon immunization they generally respond with a vigorous cytotoxic T cell response to SV40 T antigen. These data suggest that specific immune tolerance to the product of an integrated viral oncogene may be induced, and is likely a reflection of the time in development at which the gene product first appears. Immune tolerance or responsiveness to the endogenous oncogene product may in turn play a role in the tumorigenic potential of such genes.
利用来自两个不同的猴病毒40（SV40）转基因品系的小鼠（这两个品系源自注射相同基因构建体）评估了对SV40 T抗原产生免疫反应的能力。我们的研究表明，在一个SV40转基因品系中，对SV40 T抗原存在功能性免疫耐受，该品系在7月龄时会持续发生脉络丛肿瘤。在这些动物的血清中检测不到针对SV40 T抗原的抗体；此外，尽管在适当免疫时它们对痘苗病毒能产生正常的CTL反应，但来自该品系的小鼠在初次或二次用该病毒免疫后无法产生SV40特异性CTL。相比之下，我们发现来自肿瘤发生率较低的第二个转基因品系的小鼠能够对SV40 T抗原产生体液反应，并且在免疫后它们通常会对SV40 T抗原产生强烈的细胞毒性T细胞反应。这些数据表明，对整合的病毒癌基因产物的特异性免疫耐受可能被诱导，并且很可能反映了基因产物首次出现时的发育时间。对这种内源性癌基因产物的免疫耐受或反应性可能反过来在这类基因的致瘤潜力中发挥作用。
