GENETICALLY CONTROLLED MECHANISMS OF RECOVERY FROM FRIEND VIRUS-INDUCED LEUKEMIA

从朋友病毒引起的白血病中恢复的基因控制机制

• 批准号: 3960431
• 负责人: B W CHESEBRO
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3960431
• 关键词: AIDS; Friend leukemia; Friend virus; T lymphocyte; antibody neutralization test; antigen antibody reaction; antitumor antibody; antiviral antibody; cellular immunity; gene expression; genetic manipulation; genetic mapping; helper T lymphocyte; histocompatibility antigens; histocompatibility gene; host neoplasm interaction; humoral immunity; immune response genes; immunofluorescence technique; immunogenetics; immunosuppression; major histocompatibility complex; microorganism immunology; molecular oncology; monoclonal antibody; neoplasm /cancer genetics; neoplasm /cancer immunology; neoplasm /cancer remission /regression; neoplasm /cancer vaccine; plasmids; radioimmunoassay; tissue /cell culture; vaccinia virus; viral leukemia; viral vaccines; virus antigen; virus genetics; virus related neoplasm /cancer

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.

该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 小鼠红白血病作为人类逆转录病毒疾病， 艾滋病和某些白血病。 在继续研究H-2复合物在FV恢复中的作用时， 在白血病中，我们发现FV诱导的非特异性免疫抑制是 受H-2基因型影响较大。 在绘图实验中，H-2D 次区域在这一现象中似乎至关重要。 同一次区域 在FV白血病的自发恢复中也是最重要的。 然而，在这方面， 自发恢复和对免疫抑制的抵抗并不总是 相关，因为H-2D（d/B）基因型小鼠未能从 白血病，即使他们没有出现免疫抑制。 在该项目的第二阶段，我们研究了使用重组 表达FV包膜基因以诱导保护的牛痘病毒载体 挑战FV。 攻毒前， 通常检测不到，大多数挑战小鼠成功地 感染了 然而，在接种疫苗的小鼠中， 在攻击后约10天发生。 接种疫苗似乎可以保护 通过引发病毒特异性T细胞， Fv攻击后的二次免疫应答。 这种次要反应 包括中和性体液抗体和细胞溶解性T 淋巴细胞 这些效应器在保护中的确切作用是现在 在研究中