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Complementary role of HCV and HIV in T-cell activation and exhaustion in HIV/HCV coinfection.

Feuth, Thijs; Arends, Joop E; Fransen, Justin H; Nanlohy, Nening M; van Erpecum, Karel J; Siersema, Peter D; Hoepelman, Andy I M; van Baarle, Debbie.
PLoS One; 8(3): e59302, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23555014


To investigate whether T-cell activation and exhaustion is linked to HCV- and HIV disease parameters in HIV/HCV infected individuals, we studied T-cell characteristics in HIV/HCV coinfected patients and controls.


14 HIV/HCV coinfected, 19 HCV monoinfected, 10 HIV monoinfected patients and 15 healthy controls were included in this cross-sectional study. Differences in expression of activation and exhaustion markers (HLA-DR, CD38, PD-1, Tim-3 and Fas) and phenotypic markers on CD4(+) and CD8(+) T-cells were analysed by flow cytometry and were related to HCV disease parameters (HCV-viremia, ALT and liver fibrosis).


Frequencies of activated CD4(+) and CD8(+) T-cells were higher in HIV/HCV-coinfected compared to healthy controls and HCV or HIV mono-infected individuals. Coinfected patients also showed high expression of the exhaustion marker PD-1 and death receptor Fas. In contrast, the exhaustion marker Tim-3 was only elevated in HIV-monoinfected patients. T-cell activation and exhaustion were correlated with HCV-RNA, suggesting that viral antigen influences T-cell activation and exhaustion. Interestingly, increased percentages of effector CD8(+) T-cells were found in patients with severe (F3-F4) liver fibrosis compared to those with no to minimal fibrosis (F0-F2).


HIV/HCV coinfected patients display a high level of T-cell activation and exhaustion in the peripheral blood. Our data suggest that T-cell activation and exhaustion are influenced by the level of HCV viremia. Furthermore, high percentages of cytotoxic/effector CD8(+) T-cells are associated with liver fibrosis in both HCV monoinfected and HIV/HCV coinfected patients.
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