DENDRITIC CELL IMMUNIZATION OF PRETERM NEONATES

描述：（由申请人提供）

DESCRIPTION: (Provided by Applicant) Background: Dendritic cells are antigen presenting cells that play a critical role in regulation of adaptive immunity. Recently, methods have become available to isolate these cells from a variety of sources including cord blood, peripheral blood, and bone marrow. This has sparked interest in potential therapeutic use of these cells. Objectives: The primary objective of this proposal is to determine the feasibility of using cord blood derived dendritic cells as agents for prevention and treatment of infectious diseases in preterm infants. Specific aims are 1) to characterize freshly isolated and culture-derived dendritic cells generated from umbilical cord blood and adult peripheral blood, 2) to evaluate the functional capabilities of neonatal dendritic cell as antigen presenting cells, and 3) to develop practical methods for autologous DC isolation, storage, and antigen loading. Methods: Dendritic cells will be obtained from cord blood and adult blood using immunomagnetic separation techniques. Freshly isolated and culture-derived cord and adult dendritic cells will be compared for surface expression of lineage markers, major histocompatibility molecules, adhesion molecules, co-stimulatory molecules and cytokine receptors. Also, cord and adult dendritic cells will be evaluated for their functional capabilities including their ability to induce naive T cell activation and proliferation and to stimulate B cell maturation into antibody producing plasma cells. Health Relatedness: Infectious diseases represent a significant problem for very low birth weight (VLBW) infants hospitalized in Newborn Intensive Care Units (NICU). Approximately 25 percent of VLBW neonates (birth weight between 500 and 1500 grams) in the NICU experience at least one documented episode of sepsis during their hospital course. Prolonged hospitalization with exposure to resistant organisms and multiple invasive procedures, in the presence of immunologic immaturity renders these infants vulnerable to hospital-acquired infections. Dendritic cells may be ideal vehicles for immunization against infectious agents. Dendritic cells have been shown to present bacterial and viral antigens to T cells in vitro. Animal studies are encouraging as antigen pulsed dendritic cells are efficacious in providing protective immunity at a level equal to or greater than that established by conventional adjuvant vaccines. To date, studies in humans have been limited phase I/II to investigations in adult volunteers and in patients with advanced malignant diseases.