Impeding PD-1

Programmed death I (PD-1), an inhibitory receptor on immune system cells, has long been known to play an important dual role in immune regulation: Preventing the immune system from attacking the self and keeping an activated immune system in check.

In 2006, however, Rafi Ahmed, of the Emory University School of Medicine, and colleagues discovered that the PD-1 pathway could also be exploited by pathogens to repress normal T cell function during chronic viral infection. In mice infected with lymphocytic choriomeningitis virus (LCMV), Ahmed found PD-1 upregulated in functionally-impaired CD8 T cells. The team then showed that preventing PD-1 activation by blocking its ligands with antibodies restored T cell function and decreased viral load in the mice.1 Scientists had previously believed that T cells suffered irreversible dysfunction during chronic disease. Suddenly, there was the possibility of rescue.

The research was immediately extended to human chronic viral disease. Seven months after ...