Green W R
J Immunol. 1987 Mar 1;138(5):1602-6.
Previously, we reported that the generation of cytolytic T lymphocytes (CTL) specific for syngeneic tumors induced by AKR/Gross leukemia viruses was under multi-gene control. Thus, although carrying the required immune response gene(s) encoded by the H-2b haplotype and characteristic of responder strains such as C57BL/6, AKR.H-2b congenic mice failed to mount antiviral CTL responses. Young adult AKR.H-2b:Fv-1b "doubly congenic" mice, however, were able to generate specific anti-AKR/Gross virus CTL activity. These results demonstrated that the positive effect of MHC-encoded immune response gene control could be overcome by the action of the Fv-1n allele. The responder status of the B6.Fv-1n congenic, however, indicated that this Fv-1n-mediated inhibition was dependent on the interaction of Fv-1n with another gene(s) encoded by the AKR background. The results of experiments performed with AKXL recombinant inbred mice further suggested that a single additional genetic locus, encoding the Akv-1 provirus, was necessary along with Fv-1n to cause inhibition of antiviral CTL generation. Here we show that the responsiveness of AKR.H-2b:Fv-1b mice is dependent on their age. Thus, with moderate aging these doubly congenic mice converted to a nonresponder status with respect to anti-AKR/Gross virus CTL production: 85% of mice less than or equal to 9 wk of age responded compared with 0% of mice greater than 9 wk old. As with nonresponder AKR.H-2b mice, an inverse correlation was observed between CTL responsiveness and the expression of CTL-defined viral antigens by normal cells. Namely, spleen cells from young AKR.H-2b:Fv-1b mice showed little or no expression of such viral antigens, whereas with moderate aging there was a steady increase in their display. These results are discussed with reference to possible mechanisms of unresponsiveness of AKR.H-2b vs moderately aged AKR.H-2b:Fv-1b mice, and with respect to the utility of this system as a model for naturally occurring retrovirus infections and the interactions of retroviruses with the immune system.
此前，我们报道过，由AKR/格罗斯白血病病毒诱导产生的针对同基因肿瘤的细胞毒性T淋巴细胞（CTL）的生成受多基因控制。因此，尽管携带由H-2b单倍型编码的所需免疫反应基因，且具有如C57BL/6等反应品系的特征，但AKR.H-2b同源基因小鼠未能产生抗病毒CTL反应。然而，年轻成年的AKR.H-2b:Fv-1b“双重同源基因”小鼠能够产生特异性抗AKR/格罗斯病毒CTL活性。这些结果表明，MHC编码的免疫反应基因控制的积极作用可被Fv-1n等位基因的作用所克服。然而，B6.Fv-1n同源基因的反应状态表明，这种Fv-1n介导的抑制依赖于Fv-1n与由AKR背景编码的另一个基因的相互作用。用AKXL重组近交系小鼠进行的实验结果进一步表明，除了Fv-1n外，还需要一个额外的单基因座，即编码Akv-1前病毒的基因座，才能导致抗病毒CTL生成受到抑制。在此我们表明，AKR.H-2b:Fv-1b小鼠的反应性取决于其年龄。因此，随着适度衰老，这些双重同源基因小鼠在抗AKR/格罗斯病毒CTL产生方面转变为无反应状态：小于或等于9周龄的小鼠中有85%有反应，而大于9周龄的小鼠中这一比例为0%。与无反应的AKR.H-2b小鼠一样，在CTL反应性与正常细胞表达的CTL定义的病毒抗原之间观察到负相关。也就是说，年轻的AKR.H-2b:Fv-1b小鼠的脾细胞几乎不表达或不表达此类病毒抗原，而随着适度衰老，其表达量稳步增加。我们将结合AKR.H-2b与适度衰老的AKR.H-2b:Fv-1b小鼠无反应的可能机制，以及该系统作为自然发生的逆转录病毒感染模型以及逆转录病毒与免疫系统相互作用模型的实用性来讨论这些结果。
