GENETICALLY CONTROLLED MECHANISMS OF RECOVERY FROM FRIEND VIRUS-INDUCED LEUKEMIA

这个项目的目标是了解基因控制的 逆转录病毒诱导的宿主防御机制 疾病 在这项工作中，我们一直在研究自发的， 使用Friend病毒的保护性免疫的恢复和产生 复合物（FV）诱导的小鼠红白血病作为人类的模型 逆转录病毒疾病，包括艾滋病和某些白血病。 以前的实验表明，两种易感性病毒- 诱导的免疫抑制和缺乏自发 H-2D亚区影响白血病的恢复。 更 最近的数据显示， 保护性免疫的产生是由H-2l介导的， 次区域。 这一点在免疫小鼠中得到了明确的证明， 用表达FV的活重组牛痘病毒接种 包膜基因 我们最新的实验表明， 区域调节用FV包膜致敏T淋巴细胞的能力 抗原 H-2l基因通过以下方式影响这种免疫启动： 控制巨噬细胞和其他细胞呈递 FV能正确地将抗原包被到特异性T淋巴细胞上。 这 在体外直接证明了其机制， 只有适当的抗H-2l抗体才能抑制呈递 克隆抗体 类似的基因调控影响是 可能存在于人类中，并可能影响疫苗的效力， 是针对人类逆转录病毒研发的

The goal of this project is to understand genetically controlled mechanisms involved in host defense against retrovirus-induced disease. In this work we have been studying both spontaneous recovery and generation of protective immunity using Friend virus complex (FV)-induced erythroleukemia in mice as a model for human retroviral diseases including AIDS and certain leukemias. Previous experiments indicated that both susceptibility virus- induced immunosuppression and lack of ability to spontaneously recover from leukemia were influenced by the H-2D subregion. More recent data now shows that the predominant genetic influence on generation of protective immunity is mediated by the H-2l subregion. This was specifically documented in mice immunized by inoculation with live recombinant vaccinia virus expressing the FV envelope gene. Our latest experiments indicate that the H-2l region regulates ability to prime T lymphocytes with FV envelope antigens. The H-2l gene influences this immunological priming by controlling the ability of macrophages and other cells to present FV envelop antigens correctly to the specific T lymphocytes. This mechanism was directly demonstrated in vitro and antigen presentation could be inhibited only by appropriate anti-H-2l monoclonal antibodies. Similar genetic regulatory influences are likely to exist in humans and may affect potency of vaccines being developed against human retroviruses.