CD8(+) T-Cell Responses in Acute Hepatitis C Virus Infection

Abstract

Hepatitis C virus (HCV) infects approximately 170 million people worldwide and is a major cause of life-threatening liver diseases such as liver cirrhosis and hepatocellular carcinoma. Acute HCV infection often progresses to chronic persistent infection, although some patients recover spontaneously. The divergent outcomes of acute HCV infection are known to be determined by differences in virus-specific T-cell responses among patients. Of the two major T-cell subsets, CD8(+) T-cells are known to be the key effector cells that control viral infections via cytolytic activity and cytokine secretion. Herein, we review various aspects of HCV-specific CD8(+) T-cell responses in acute HCV infection. In particular, we focus on timing of CD8(+) T-cell responses, relationship between CD8(+) T-cell responses and outcomes of acute HCV infection, receptor expression on CD8(+) T-cells, breadth of CD8(+) T-cell responses, and viral mutations.

Keywords: CD8+ T-cell; acute infection; function; hepatitis C virus; outcome.

Figure 1

Virologic courses and kinetics of CD8⁺ T-cell responses in acute HCV infection. (A–C) Three virologic patterns of acute HCV infection (11). (D) Kinetics of CD8⁺ T-cell response in acute HCV infection (20, 21). The frequency of HCV-specific CD8⁺ T-cells in the blood and mRNA levels of CD8β and IFN-γ in the liver are presented. The appearance of HCV-specific CD8⁺ T-cells in the blood coincides with the increase in mRNA levels of CD8β and IFN-γ in the liver and with serum ALT elevation and a decrease in HCV RNA titer.

Figure 2

Sequence of events during HCV-specific CD8⁺ T-cell responses in blood and liver throughout acute HCV infection.

Figure 3

Virologic course and kinetics of CD8⁺ T-cell responses after HCV challenge in successfully vaccinated hosts. (A) Virologic course after HCV challenge in successfully vaccinated hosts (23). HCV RNA was transiently detected and disappeared, and serum ATL was also transiently elevated. (B) Kinetics of CD8⁺ T-cell responses after HCV challenge in successfully vaccinated hosts (19, 24). Early CD8⁺ T-cell responses are shown by the frequency of HCV-specific CD8⁺ T-cells in the blood and mRNA levels of CD8β and IFN-γ in the liver.