<figcaption> Credit: © Eye of Science / Photo Researchers, Inc.</figcaption>
Credit: © Eye of Science / Photo Researchers, Inc.

The paper:
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)

The finding:
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.

The impact:
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.

The application:
"There are obvious parallels to HIV, and we had to start working on it right away," says Richard...

The numbers:
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

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