Immune control of SIVagm replication in vivo

描述（由申请人提供）：亚洲猕猴在感染了非洲非人灵长类动物特有的慢病毒后患上了一种类似艾滋病的疾病。然而，非洲猴子尽管持续和终身感染相同的病毒，却没有发病。对非洲猴子对慢病毒引起的疾病产生自然抗性的机制的清楚了解，可能会支持目前开发艾滋病疫苗的战略，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的两种非洲绿猴来研究这一现象。利用我们之前开发的单克隆抗体诱导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在这些物种中对疾病的自然抗性中的作用。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. 确定体液免疫反应在通过消耗B淋巴细胞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感染SIVagm的过程。

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.