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CORRESPONDENCE G.J.F.: gordon_freeman{at}dfci.harvard.edu

ABSTRACT
The programmed death (PD)-1–PD-1 ligand (PD-L) pathway, which is part of the B7–CD28 family, consists of the PD-1 receptor and its two ligands PD-L1 and PD-L2. Engagement of PD-1 by its ligands inhibits immune responses, and recent work has shown that PD-1 is highly expressed on exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Blockade of this pathway reinvigorates the exhausted T cells, allowing them to expand and produce effector cytokines, raising the issue of whether this pathway has been exploited by a variety of viruses during chronic infection. New studies now extend these observations to HIV infection and human disease.

E.J.W. is at Immunology Program, The Wistar Institute, Philadelphia, PA 19104.

R.A. is at Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322.

A.H.S. is at Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115.

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