T-cell revival

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The paper:

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 Koup at the National Institute of Allergy and Infectious Diseases. He and his colleagues followed up in 2006 to show that blocking PD-1 could restore some T-cell function in human cells infected with HIV ( J Exp Med, 203:2223-7, 2006). "We and other groups are getting ready to do the blockade in SIV-infected monkeys," says Ahmed.

The warning:
PD-1 is thought to shut down T-cell response to avoid cytotoxicity. Koup cautions, "It may be dangerous to go in and turn off PD-1 in all T cells. Somehow, if we're going to regulate the PD-1/PD-L1 and PD-L2 axis, we'd like to do it in a specific manner."ﾠﾠ