Population Council | 2004 Annual Report | Investigating the Immune System's Response to HIV

2004 ANNUAL REPORT

Biomedicine
Investigating the Immune System’s Response to HIV

Research on the immune system’s response to HIV being conducted in the laboratory of Population Council immunologist Melissa Pope could one day become the basis for an anti-HIV vaccine or next-generation microbicide. Microbicides are products, likely to be produced in the form of a gel, foam, or cream, that would substantially reduce the transmission of HIV when applied before sexual intercourse.

Photograph of T cells and dendritic cells

Pope and her colleagues exposed dendritic cells
to virus and then mixed them with CD4 T cells.
Microscopic analysis revealed virus-positive
“bridges” between dendritic cells and T cells as
the dendritic cell (upper right) passes virus to the
T cell (lower right). Subsequent spread of virus
between T cells (left) is also shown in this photo.

Pope studies immune system cells known as dendritic cells. These cells engulf viruses and degrade them into protein fragments, called antigens. Dendritic cells display the antigens on their outer membranes; other immune system cells recognize the antigens and launch a potent immune response. This response does not happen efficiently during HIV infection, however. Paradoxically, the meeting instead spurs an increase in viral replication.

Pope and her collaborators investigated binding of HIV to human cervical tissue cells in a Petri dish. The team found that different molecular receptors play a role in the infection of cervical cells, which do not migrate, and of dendritic cells, which do. This confirmed earlier work carried out using blood-derived dendritic cells. The migratory nature of dendritic cells can ferry HIV to infect and decimate other cells of the immune system, such as CD4 T cells. “Microbicidal preparations should target all receptors that are exploited by HIV as well as proteins on the surface of HIV,” says Pope. Pope’s laboratory and the lab of virologist David Phillips are collaborating on a number of microbicide-related projects.

An effective vaccine would induce activated dendritic cells to launch a proper immune response against HIV. Increasing the number of circulating dendritic cells, which usually make up only 1 percent of circulating immune system cells, may be a key step in producing a workable vaccine. Pope and her colleagues investigated the effects of Flt3L, a molecule that has been shown to trigger the movement of dendritic cells (and their precursors) from bone marrow into the rest of the body. “We found that treatment for as little as five to seven days was effective at increasing the dendritic cell count,” says Pope. Her team is also investigating ways to activate circulating dendritic cells more effectively to improve their ability to stimulate anti-HIV immunity following vaccination.

“Our research is illuminating ways of keeping dendritic cells from transporting or becoming infected with HIV, while at the same time improving their ability to initiate a powerful attack on the virus,” says Pope.

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