Immune control of SIVagm replication in vivo

描述（由申请人提供）：亚洲猕猴在感染慢病毒后发生艾滋病样疾病，慢病毒可局部感染非洲非人灵长类动物。然而，非洲猴子没有发展疾病，尽管持续和终身感染相同的病毒。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见解。在这个建议中，我们将利用感染SIVagm的两种非洲绿色猴来研究这种现象。使用我们以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应答对这些物种中所见的自然抗病性的作用。具体来说，我们将：1。在非洲绿色猴中确定由CD8+淋巴细胞介导的适应性免疫应答在控制SIVagm病毒血症和疾病进展中的作用。2.通过B淋巴细胞耗竭，确定体液免疫应答在影响相同感染过程中的作用。3.评估消除细胞和体液适应性免疫应答是否会影响非洲绿色猴的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.