Immune control of SIVagm replication in vivo

SIVagm 体内复制的免疫控制

• 批准号: 7062226
• 负责人: Joern E. Schmitz
• 金额: $ 67.38万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7062226
• 关键词: B lymphocyte; Lentivirus; emotions; immune response; immunity; infection; role

DESCRIPTION (provided by applicant): Asian macaques develop an AIDS-like disease upon infection with lentiviruses that endemically infect African nonhuman primates. However, African monkeys fail to develop disease despite persistent and life-long infection with the same viruses. A clear understanding of the mechanisms responsible for the natural resistance of African monkeys to lentivirus-induced disease might support current strategies to develop AIDS vaccines or provide insight into new treatment modalities for HIV infection. In this proposal, we will utilize the infection of two African green monkey species infected with SIVagm to study this phenomenon. Using the models of monoclonal antibody-induced depletion of CD8+ lymphocytes and B cells which we developed previously, we will assess the role of adaptive immune responses to the natural resistance to disease seen in these species. Specifically, we will: 1. Determine the role of adaptive immune responses mediated by CD8+ lymphocytes in controlling SIVagm viremia and disease progression in African green monkeys. 2. Determine the role of humoral immune responses in affecting the course of the same infections by depletion of B lymphocytes. 3. Assess whether abolishing both cellular and humoral adaptive immune responses will affect the course of SIVagm infection of African green monkeys.

描述（由申请人提供）：亚洲猕猴在感染当地感染非洲非人类灵长类动物的慢病毒后，会患上类似艾滋病的疾病。然而，尽管非洲猴子持续且终生感染相同病毒，但并未患上疾病。清楚地了解非洲猴子对慢病毒引起的疾病的自然抵抗力的机制可能会支持当前开发艾滋病疫苗的策略或为艾滋病毒感染的新治疗方式提供见解。在本提案中，我们将利用感染 SIVagm 的两种非洲绿猴物种来研究这一现象。使用我们之前开发的单克隆抗体诱导的 CD8+ 淋巴细胞和 B 细胞耗竭模型，我们将评估适应性免疫反应对这些物种的自然抗病能力的作用。具体来说，我们将： 1. 确定 CD8+ 淋巴细胞介导的适应性免疫反应在控制非洲绿猴 SIVagm 病毒血症和疾病进展中的作用。 2. 通过消耗 B 淋巴细胞，确定体液免疫反应在影响相同感染过程中的作用。 3. 评估取消细胞和体液适应性免疫反应是否会影响非洲绿猴的 SIVagm 感染过程。