D.L. Barber et al., "Restoring function in exhausted CD8 T cells during chronic viral infection," Nature, 439:682-7, 2006. (Cited in 97 papers)
Rafi Ahmed at Emory Vaccine Center in Atlanta and colleagues examined microarrays from T cells that lose function during chronic lymphocytic choriomeningitis, a viral infection of immune cells that causes meningitis. They found a number of gene-expression changes. The most striking was an upregulation of the inhibitory receptor, programmed death 1 (PD-1) and its ligand. Blocking their interaction improved T-cell function.
Until this study, "no one had shown [that] you could interfere immunologically and restore T-cell function," Ahmed says. The cells made more cytokines and were able to lyse targets, he adds.
"There are obvious parallels to HIV, and we had to start working on it right away," says Richard...
|Effects of PD-1 blockade|
|700||Percent increase in CD8 T cells|
|≥30||Point increase in percentage of cells producing IFN-γ|
|~50||Percent decrease of viral titers in serum, spleen, lung, and liver|