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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