ÿþ<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd"> <html> <head> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <title>EASL 2010 - Poster Presentations</title> <link rel="stylesheet" type="text/css" href="style.css"> </head> <body> <table width="750" align="center" border="0" cellspacing="0" cellpadding="0" class="MainTable"> <tr> <td><img src="http://www2.kenes.com/liver-congress/PublishingImages/top_ei.jpg" width="760" height="129" /></td> </tr> <tr> <td class="content"><h1>Poster Presentations</h1> <P><b>Session Title:</b> Category 10. LIVER IMMUNOLOGY<br><b>Presentation Date:</b> Apr 15, 2010</P><h2 align='left'><B>HEPATITIS C CO-INFECTION SENSITIZES CD4<SUP>+</SUP> T CELLS TOWARDS FAS-INDUCED APOPTOSIS IN HIV-POSITIVE PATIENTS</B></h2> <p align='left'><b>C. Körner</b>*, F. Tolksdorf, D. Schulte, B. Krämer, M. Coenen, A. Glässner, M. Eisenhardt, T. Sauerbruch, J. Nattermann, J. Rockstroh, U. Spengler<br> <em>Internal Medicine I, University of Bonn, Bonn, Germany. *christian.koerner@ukb.uni-bonn.de</em></p><br> <p align='justify'><b><b>Introduction: </b></b> Recently, we identified increased rates of CD4<sup>+</sup> T cell apoptosis in HCV-infected HIV(+) patients as a potential mechanism contributing to accelerated progression towards AIDS and increased mortality in patients with HIV/HCV co-infection. <br>Although, the underlying mechanisms remain unclear, changes of receptor-induced apoptosis could be a potential cause of this effect. Therefore, we studied expression and function of Fas ligand (FasL) and its corresponding death receptor Fas on CD4<sup>+</sup> T cells in HIV/HCV co-infection.<br><b><b>Methods: </b></b> A total of 130 patients were enrolled in this study including 15 HCV-mono-infected, 54 HIV-mono-infected, 61 HCV/HIV-co-infected patients and 15 healthy controls (HC). Serum levels of soluble FasL were detected by ELISA. Surface expression of Fas and FasL were determined on CD4<sup>+</sup> T cells by flow cytometry. FasL-induced apoptosis was analyzed by incubating isolated PBMC from patients and controls with rhFasL followed by measuring CD4<sup>+</sup> T cell apoptosis.<br><b><b>Results: </b></b> HIV and HCV mono-infection were associated with significantly enhanced surface expression of Fas (HC: 38±3.8; HIV: 60±3.6, p< 0.001; HCV: 63±7.9, p< 0.01). Of note, highest Fas expression was detected in HIV/HCV-co-infected patients (HIV/HCV: 88±8.2, p< 0.05 vs. HIV and HCV). In addition, Fas expression was strongly correlated with low CD4<sup>+</sup> T cell counts in HIV-positive patients (p< 0.001).<br>In contrast, elevated levels of soluble (HIV: 131±18 pg/ml; HIV/HCV: 189±42) and cellular FasL (HIV: 84±4; HIV/HCV: 85±10) were found only in patients with HIV infection (p>0.05 each vs. HC), but not in patient with hepatitis C alone (sFasL: 73±19; cFasL: 64±7). Importantly, enhanced Fas expression in HCV/HIV co-infection rendered CD4<sup>+</sup> T cells more susceptible towards FasL-induced apoptosis (p< 0.01).<br>Furthermore, while effective HAART normalized serum levels of sFasL and expression of cellular FasL in HIV- and HIV/HCV-co-infected patients, expression of Fas decreased only slightly and still remained significantly elevated as compared to healthy controls (p< 0.01 each vs. HC).<br><b><b>Conclusions: </b></b> Our findings suggest a synergistic mechanism in HIV/HCV co-infection between upregulation of Fas expression on CD4<sup>+</sup> T cells and HIV-induced elevated levels of cellular and soluble FasL. Together, both effects contribute to enhanced apoptosis of CD4<sup>+</sup> T cells, which has been observed in HIV/HCV co-infection.<br></p> <br><a href='Session-P01-10.htm'>Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>