Immune control of SIVagm replication in vivo

描述(申请人提供)：亚洲猕猴感染慢病毒后会发展成一种类似艾滋病的疾病，慢病毒会地方性地感染非洲非人类灵长类动物。然而，尽管非洲猴子持续并终生感染相同的病毒，但它们仍未患上疾病。清楚地了解非洲猴子对慢病毒引起的疾病的天然抵抗力的机制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洞察。在这项建议中，我们将利用感染SIVagm的两个非洲绿猴物种的感染来研究这一现象。利用我们之前建立的单抗诱导CD8+淋巴细胞和B细胞耗竭的模型，我们将评估获得性免疫反应在这些物种对疾病的自然抵抗力中的作用。具体地说，我们将：1.确定CD8+淋巴细胞介导的获得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.通过耗尽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.评估废除细胞和体液获得性免疫反应是否会影响非洲绿猴的SIVagm感染过程。

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.