Rappaport and his collaborators at the Center have been focusing on the role of macrophages--large, long-lived cells of the immune system that travel throughout the body and ingest foreign antigens to protect against infection--in the development of HIV dementia complex.
"Basically, HIV infection of the central nervous system and the brain is really the cause of severe HIV dementia, and currently 10 percent of AIDS patients get this type of dementia," says Rappaport. "This figure has dropped from 20 to 30 percent because of the success of highly aggressive anti-retroviral therapy. This figure might increase if drug therapy begins to fail in patients who are on therapeutic regimens for longer periods of time.
"For many years, there has been a 'Trojan Horse' model, which holds that these macrophages might enter the brain early during infection, secretly carrying the AIDS virus and allowing the long-term resident macrophages of the brain [the microglia] to be infected," says Rappaport.
Rappaport believes that, during AIDS, the major invasion of HIV occurs late in the disease. Trafficking and production of macrophages in the brain increase during this time. He hypothesizes that these increases come from bone marrow, because, he says, "there's an activated subset in blood that goes way up in HIV patients with dementia. These macrophages are more invasive in other organs as well.
"So the grant we've received is really to look at the issue of generation and trafficking of these macrophages, where they're being expanded in AIDS, and how they get into the brain," he adds. "Also, we want to determine how they get i
Contact: Preston M. Moretz