Serious CNS dysfunction is the preeminent complication of HIV infections of infants and children. By elucidating the initial immunopathologic mechanisms of perinatal HIV subsequent CNS pathology. Epidemiologic data suggest that the fetus and neonate may be uniquely susceptible to HIV infections and disease progression, especially CNS dysfunction. As only a relatively small proportion of lymphocytes from HIV infected individuals show the presence of virus, disease progression may also be due to noninfectious effects of HIV-derived soluble products on the immune system. We have shown that the envelope proteins of HIV are immunoregulatory and can suppress the immune functions of the infected host. This project will assess lymphocyte responses of the fetus and neonate to a panel of recombinant and synthetic HIV-specific peptides. By comparing responses of adult donor lymphocytes we may identify mechanisms which render the fetus or neonate uniquely susceptible to HIV infection, CNS dysfunction and the immunosuppressive effects of HIV peptides. We shall utilize a defined in vitro model system consisting of cord blood or adult peripheral lymphocytes pretreated with recombinant and synthetic HIV peptides and subsequently examined for various functional activities. Cord blood donors will be stratified into mothers at high and low risk of HIV infection. We shall also attempt to stratify our data on the basis of the ethnicity or race of the cord blood donors to see if immunologic function may be associated with this variable. The high risk cohort will be further divided into HIV+ and HIV- groups. The responses of cord lymphocytes to HIV peptides will be compared to lymphocyte responses from healthy adult donors and possibly children from different age groups. Lymphocytes preincubated with HIV peptides will be then treated in vitro with several biological modifier substances to identify potential agents capable of reversing the adverse effects of HIV peptides. These studies may define unique immunologic properties of the perinatal period which increase the susceptibility of the fetus or neonate to HIV infection and progression to the CNS consequences of pediatric AIDS. The identification of agents useful in the prophylaxis of the high-risk fetus against HIV infections and/or disease progression involving the CNS could be derived from this project.
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