Early immune responses in SIV-infected newborn macaques: Characterization of the natural killer cells
Maternal transmission of human immunodeficiency virus type 1 (HIV-1) accounts for most cases of pediatric HIV-1 infection. Approximately 75 to 85% of perinatally HIV-1-infected infants develop a slowly progressive course of infection with a slow CD4 decline. In contrast, 10 to 25% of infected infants develop rapidly progressive infection with early CD4+ T-cell depletion followed by death within the first two years of life. The mechanisms whereby the first group maintains some control over viral replication are not understood. Scientists have speculated that susceptibility of children to AIDS is due to the "immaturity of their immune system". However, a variety of ethical and practical considerations inherent in human clinical studies make it difficult to rigorously address these issues in Pediatric AIDS. In this study, we have used newborn monkeys infected with a pathogenic or non-pathogenic strain of simian immunodeficiency virus (SIV) to carefully define developmental changes in T cells' composition and function compared to uninfected neonates. Specific aims include: 1) To investigate the dynamics and activation of SIV-specific T-cell responses in early infection in neonatal macaques; 2) To examine if there are any functional impairments of the response; 3) To characterize the distribution of SIV-specific T-cells in specific host tissues; and, 4) To investigate and characterize the role of Natural Killer cells in early SIV-infection. This study should enhance the basic understanding of HIV/AIDS pathogenesis and immune responses in infected neonatal macaques.