Discoveries
Study suggests way to re-energize immune response
Gordon Freeman, PhD
Investigators at Dana-Farber and Emory University have identified a potentially straightforward way of "re-energizing" the immune system's attack on persistent viral infections, raising hopes of more effective therapies for people harboring long-term infections ranging from hepatitis to HIV, the virus that causes AIDS.
In chronic viral infections, the immune system's CD8 T cells – some of which retain a "memory" of foreign organisms they've encountered – fail to sustain their attack on the infection for more than a month or so. Rafi Ahmed, PhD's lab at Emory has shown that such cells become less active, or "exhausted." In the new study, conducted with mouse cells, Dana-Farber's Gordon Freeman, PhD, and his colleagues traced the problem to a gene that turns off CD8 T cells' infection-fighting drive.
They made the discovery by measuring the activity of thousands of genes in normal memory CD8 T cells in mice and in exhausted versions of those cells. They found that a gene known as PD-1 was much more active in the exhausted cells. When they used an antibody to block the PD-1 protein's ability to latch onto another molecule, the CD8 cells' response to infection was reactivated.
If human CD8 T cells are found to operate by a mechanism similar to that in mice, the new findings may offer a simple immunological strategy for treating chronic viral infections. Freeman's lab is also exploring whether anticancer T cells become exhausted in various types of tumors and in HIV-infected individuals – and whether their disease attack can be re-ignited.
