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JCI online early table of contents: Nov. 15, 2010
Date:11/15/2010

e proportion of patients who become infected with hepatitis C virus (HCV), the virus evades the anti-viral immune response to establish a persistent infection. In these individuals, the function of HCV-specific immune cells known as CTLs is impaired as a result of inhibitory signals emanating from proteins such as Tim-3 and PD-1 on their surface. A team of researchers, led by Hugo Rosen, at the University of Colorado Denver, Aurora, has now generated data that suggest that blocking the inhibitory proteins Tim-3 and PD-1 might provide a new approach to treating individuals with a persistent HCV infection.

The team determined that expression of PD-1 and Tim-3 on HCV-specific CTLs was characteristic of individuals acutely infected with HCV who were more likely to develop persistent HCV infection. Importantly, blockade of either PD-1 or Tim-3 enhanced the in vitro proliferation of HCV-specific CTLs, while blockade of Tim-3 increased the ability of these cells to kill cells expressing HCV proteins. The authors therefore conclude that coexpression of PD-1 and Tim-3 on HCV-specific CTLs is associated with the development of persistent HCV infection and suggest that simultaneous blockade of PD-1 and Tim-3 might be therapeutically useful.

TITLE: Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity

AUTHOR CONTACT:
Hugo R. Rosen
University of Colorado Denver, Aurora, Colorado, USA.
Phone: 303.724.1858; Fax: 303.724.1891; E-mail: Hugo.Rosen@ucdenver.edu.

View this article at: http://www.jci.org/articles/view/43127?key=b248ddb642397e4495f7


PHYSIOLOGY: Patients explain exactly why we need the chemical element selenium

The trace element selenium is essential for cellular
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Contact: Karen Honey
press_releases@the-jci.org
734-546-5242
Journal of Clinical Investigation
Source:Eurekalert

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