Abstract
Multiple interferon‐stimulated genes (ISGs) involving T‐cell activation are upregulated during initial interferon‐α‐based therapy for chronic hepatitis C virus (HCV) infection. However, the long‐term impact on therapeutic outcome in patients remains unknown. In this study, the effects of anti‐HCV therapy on the surface ex‐pression of HLA‐ABC, CD86, and CD28 were longitudinally assessed. These proteins are integral membrane receptors of antigen presentation and triggering of costimulatory signals for activating CD8^+^ T cells. Peripheral blood mononuclear cells were collected at baseline and post‐treatment for 1 day, and 2, 4, 12, and 24 weeks, respectively. This treatment led to a time‐related elevation of membrane levels of HLA‐ABC and CD86 on B‐cells and monocytes in patients with a sustained response (n = 23), but not in those without (n = 8). Meanwhile, upregulation of CD28 on CD4^+^ and CD8^+^ T cells was comparable in both groups of sustained responders and non‐responders. Steady increases in the B cells' surface and intracellular HLA‐ABC were observed, thus, the surface‐to‐intracellular ratios did not alter over the period of treatment. Furthermore, multivariate analysis shows that increased HLA‐ABC on monocytes by week 12 correlates significantly with sustained response (P = 0.033). In conclusion, differential modulation of T‐cell activation ISGs, such as HLA‐ABC and CD86 might correlate with the outcome of interferon‐α‐based therapy in chronic hepatitis C patients. J. Med. Virol. 80:989–996, 2008. © 2008 Wiley‐Liss, Inc.