Margo Roberts
Grant Abstract
Elizabeth Glaser Pediatric AIDS Foundation
PG-51140 "Imaging and Function of HIV-specific T Cells in the CNS"
HIV-1 infection in infants and children can cause progressive neurologic disease resulting in impaired brain growth, loss of developmental milestones, motor abnormalities and progressive HIV-1 encephalopathy. The current understanding of HIV-1 neuropathogenesis is that HIV-1 infection of the CNS results in the production of toxic viral and/or cellular products to which the developing brain is particularly susceptible. Accumulating data support HIV-1 invasion of the CNS concurrently or nearly concurrently with acute systemic infection rather than as a late sequela of chronic infection. Therefore, optimal therapeutic strategies must target the primary infected cell type in the brain -- the microglia. The importance of such approaches is underscored by recent data indicating that CNS-resident microglia may serve as a critical anatomical reservoir for HIV. Increasingly strong evidence implicates T cells as critical mediators of peripheral anti-viral immunity. In contrast little is known about T cell responses in the brain although microglia do appear to be relatively weak antigen presenting cells. Thus, we propose to develop strategies for increasing the survival and function of HIV-specific T cells in the brain, employing well defined small animal models in which HIV antigens can be selectively expressed in CNS-resident microglia. In addition to the development of immunotherapeutic strategies for eliminating/reducing HIV-infected cells in the brain, we also propose to simultaneously lay the groundwork for tracking anti-viral T cell migration and responses in the clinical setting
01/01/2001-12/31/2002