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Biotech / Medical : MEDX ... anybody following?
MEDX 31.15-0.3%Nov 3 1:15 PM EST
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From: Icebrg9/25/2008 3:39:08 AM
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Selective expansion of a subset of exhausted CD8 T cells by {alpha}PD-L1 blockade.

Proc Natl Acad Sci U S A. 2008 Sep 22. [Epub ahead of print]
Blackburn SD, Shin H, Freeman GJ, Wherry EJ.
Immunology Program, The Wistar Institute, Philadelphia, PA 19104.

Programmed death-1 (PD-1) regulates T cell exhaustion during chronic infections. Blocking the PD-1:PD-ligand (PD-L) pathway reinvigorates exhausted CD8 T cells. Exactly how blocking PD-1:PD-L interactions improves T cell immunity, however, remains unclear. PD-1:PD-L blockade could reprogram all exhausted T cells to become antiviral effectors. Alternatively, this blockade might selectively expand a subset of exhausted T cells.

We have identified two subpopulations of exhausted CD8 T cells during chronic viral infection in mice. One subset of exhausted CD8 T cells is rescued by alphaPD-L1 blockade, whereas the other subset appears more terminally differentiated and responds poorly to PD-1:PD-L blockade. Blocking PD-1:PD-L interactions reduces spontaneous apoptosis and enhances expansion and protective immunity of the rescuable subset, but not the more terminally differentiated subset of exhausted CD8 T cells.

These results have implications for predicting clinical responses to PD-1-based therapeutic interventions and for understanding T cell dynamics during persisting infections.
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