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J Exp Med. 2006 Oct 2;203(10):2223-7. Epub 2006 Sep 25.

Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade.

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  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.


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.

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