GENETICALLY CONTROLLED MECHANISMS OF RECOVERY FROM FRIEND VIRUS-INDUCED LEUKEMIA

这个项目的主要目标是阐明 Friend逆转录病毒复合体(FV)诱导的恢复或持续 用小鼠红白血病作为人类逆转录病毒病的模型 艾滋病和某些白血病。 在继续研究H-2复合体在FV恢复中的作用 白血病，我们发现Fv诱导的非特异性免疫抑制是 受H-2基因影响较大。在测绘实验中，H-2D 在这一现象中，次区域似乎至关重要。这同一个次区域 在FV白血病的自然恢复过程中也是最重要的。然而， 自然恢复和对免疫抑制的抵抗并不总是 相关的，因为H-2D(d/b)基因的小鼠无法从 白血病，尽管他们似乎没有免疫抑制。 在这个项目的第二阶段，我们研究了一种重组的 表达FV囊膜基因的痘苗病毒载体诱导保护作用 对抗FV的挑战。在攻击之前，中和抗体是 通常检测不到，大多数受到挑战的小鼠都成功地 被感染了。然而，在接种疫苗的小鼠中，脾肿大很快就会恢复 发生在激发后10天左右。接种疫苗似乎有保护作用 通过启动病毒特异性T细胞，从而促进快速 FV攻击后的二次免疫反应。这种次要的反应 包括中和体液抗体和细胞溶解T细胞 淋巴细胞。这些效应器在保护中的确切作用现在是 正在调查中。

The main goal of this project is the elucidation of mechanisms involved in recovery from or persistence of Friend retrovirus complex (FV)-induced erythroleukemia in mice as a model for human retrovirus diseases such as AIDS and certain leukemias. In continuing studies of the role of the H-2 complex in recovery from FV leukemia, we have found that nonspecific immunosuppression induced by FV is strongly influenced by H-2 genotype. In mapping experiments, the H-2D subregion appeared to be critical in this phenomenon. This same subregion is also most important in spontaneous recovery from FV leukemia. However, spontaneous recovery and resistance to immunosuppression were not always associated, since mice of the H-2D(d/b) genotype failed to recover from leukemia even though they did not appear to be immunosuppressed. In a second phase of this project, we have studied the use of a recombinant vaccinia virus vector expressing the FV envelope gene to induce protection against challenge by FV. Before challenge neutralizing antibodies were usually not detectable, and most challenged mice were successfully infected. However, in vaccinated mice rapid recovery from splenomegaly occurred at about 10 days after challenge. Vaccination appeared to protect by priming of virus-specific T cells which then facilitated a rapid secondary immune response after Fv challenge. This secondary response included both neutralizing humoral antibody as well as cytolytic T lymphocytes. The precise role of these effectors in protection is now under investigation.