IMMUNOPATHOGENESIS OF LP-BM5 INFECTION-MURINE ACQUIRED IMMUNODEFICIENCY DISEASE

LP-BM5感染鼠获得性免疫缺陷病的免疫发病机制

• 批准号: 3748227
• 负责人: A S ROSENBERG
• 金额: --
• 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/3748227
• 关键词: B lymphocyte; MHC class I antigen; MHC class II antigen; Retroviridae; Retroviridae disease; acquired immunodeficiency; cell population study; disease /disorder model; genetic strain; graft versus host disease; immunopathology; laboratory mouse; liposomes; macrophage; polymerase chain reaction; provirus; skin; virus infection mechanism

Using a murine model of acquired immunodeficiency (MAIDS) induced by LP- BM5 retroviruses, we explored whether the presence of retrovirus resistant cells, at the time of infection, would alter the induction and progression of retroviral disease in animals harboring susceptible cellular populations. Allophenic chimeras in which one parent strain was susceptible and the other parent strain resistant to LP-BM5 retroviruses were constructed. Lymphoid chimerism of individual animals was assessed by flow cytometric techniques and the animals subsequently inoculated with the retroviral mix. The animals were assessed for time to lymphadenopathy, time to death, changes in flow cytometric parameters, and for recovery of retroviral species. These studies revealed that the presence of substantial, but less than predominant numbers of resistant cells afforded no protection against disease, with the animals developing lymphadenopathy and dying in the same time frame as fully susceptible control mice and with comparable recovery of retroviral species. However, in animals in which the predominant lymphoid population was of the resistant genotype, the animals failed to develop disease, and little or no retrovirus was recovered. Thus, it is apparent that there is a critical balance between susceptible and resistant lymphoid cells that determines whether the animals succumb to disease, or achieve long term resistance. Additional studies have been planned to elucidate the basis of the failure of suboptimal numbers of resistant cells to confer benefit and to further identify the critical resistant cellular populations responsible for conferring protection against disease.

使用LP-诱导的获得性免疫缺陷（MAIDS）小鼠模型 BM 5逆转录病毒，我们探讨是否存在逆转录病毒 在感染时，抗性细胞会改变诱导， 携带易感病毒的动物中逆转录病毒疾病的进展 细胞群体。 异基因嵌合体，其中一个亲本菌株是 对LP-BM 5逆转录病毒敏感的亲本菌株和对LP-BM 5逆转录病毒耐药的亲本菌株 构建成 评估了个体动物的拟嵌合体 通过流式细胞术技术和随后接种的动物 逆转录病毒混合物 对动物进行了时间评估， 淋巴结病，死亡时间，流式细胞术参数的变化， 以及逆转录病毒种类的回收。这些研究表明， 存在大量但少于主要数量的耐药 细胞不能提供抵抗疾病的保护， 淋巴结病和死亡在同一时间内完全易感 对照小鼠和逆转录病毒种类的恢复相当。 然而，在主要淋巴细胞群为 耐药基因型，动物未能发展疾病， 几乎没有或没有回收到逆转录病毒。因此，很明显， 是敏感和抵抗淋巴细胞之间的关键平衡 决定动物是否死于疾病， 长期抵抗 计划进行更多的研究以阐明 次优数量的耐药细胞失败的基础， 并进一步确定关键的耐药细胞 负责提供疾病防护的人群。