当前位置： SCI文献检索 > ANTIVIRAL THERAPY期刊下所有文献 > Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fas-induced apoptosis in viraemic and HAART-controlled HIV-1-positive patients.

Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fas-induced apoptosis in viraemic and HAART-controlled HIV-1-positive patients.

Abstract：

BACKGROUND:Recently, we identified increased rates of CD4(+) T-cell apoptosis in HCV-infected HIV-positive patients as a potential mechanism for enhanced mortality in patients with HIV/HCV coinfection. Since this effect might be attributed to changes in receptor-induced apoptosis, we studied expression and function of Fas ligand (FasL) and its death receptor Fas on CD4(+) T-cells in HIV/HCV coinfection. METHODS:In this cross-sectional study, we simultaneously analysed surface expression of Fas and FasL on CD4(+) T-cells and serum levels of soluble FasL in HCV/HIV-coinfected, HIV-monoinfected and HCV-monoinfected patients. Susceptibility to FasL-induced apoptosis was analysed by incubating isolated peripheral blood mononuclear cells with rhFasL followed by measuring CD4(+) T-cell apoptosis. RESULTS:HIV and HCV monoinfection were associated with significantly enhanced surface expression of Fas. Highest Fas expression was detected in HIV/HCV-coinfected patients and correlated with low CD4(+) T-cell counts. By contrast, elevated levels of soluble and cellular FasL were found only in patients with HIV infection, but not in patients with HCV infection. Importantly, enhanced Fas expression in HCV/HIV coinfection rendered CD4(+) T-cells more susceptible towards FasL-induced apoptosis. While effective HAART normalized expression and secretion of FasL in HIV-infected and HIV/HCV-coinfected patients, expression of Fas decreased only slightly and still remained significantly elevated as compared with healthy controls. CONCLUSIONS:Our findings suggest a synergistic mechanism in HIV/HCV coinfection between up-regulation of Fas expression on CD4(+) T-cells and HIV-induced elevated levels of cellular and soluble FasL. Together, both effects contribute to enhanced apoptosis of CD4(+) T-cells in HIV/HCV coinfection.

journal_name

Antivir Ther

journal_title

Antiviral therapy

authors

Körner C,Tolksdorf F,Riesner K,Krämer B,Schulte D,Nattermann J,Rockstroh JK,Spengler U

doi

10.3851/IMP1882

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

1047-55

issue

eissn

1359-6535

issn

2040-2058

journal_volume

pub_type

杂志文章

在线工具

Hepatitis C coinfection enhances sensitization of CD4(+) T-cells towards Fas-induced apoptosis in viraemic and HAART-controlled HIV-1-positive patients.