Immunological Control of Hepatitis C Virus during Acute Infection

In a majority of patients, hepatitis C virus (HCV) becomes chronic, persisting for more than 6 months after acute infection. Cellular immune responses are thought to play a major role in control of the virus and spontaneous clearance after infection. Failure of CD4 T-cell responses during acute disease is associated with viral persistence, but the dynamics of this are poorly understood.

As reported in the October 2006 Journal of Viral Hepatitis, researchers with the Institute for Immunology at the University of Munich in Germany used a novel set of Class II tetramers to study the responses of helper T-cells ex vivo (outside the body) during acute HCV infection.

The researchers analyzed HCV-specific CD4 T-cell responses in a single patient with acute hepatitis C infection. They were able to track virus-specific CD4 T-cells directly ex vivo with HLA DR4 tetramers.

Proliferative responses were absent initially, then recovered as HCV viral load dropped, but were lost again during relapse. However, longitudinal tetramer analyses showed expanded populations of antiviral CD4 T-cells throughout the course acute infection, despite lack of proliferation.

A pattern of transient CD4 T-cell proliferative responses was observed as HCV was partially controlled by the immune system. Failure to control the virus was associated with the emergence of "dysfunctional" CD4 T-cell populations.

The authors concluded that, "Failure to control HCV in acute disease may relate to the capacity to sustain efficient immune responses as the virus attempts to 'bounce back' after partial control."

10/06/06

Reference
A Ulsenheimer, M Lucas, N P Seth, and others. Transient immunological control during acute hepatitis C virus infection: ex vivo analysis of helper T-cell responses. Journal of Viral Hepatitis 13(10): 708-14. October 2006.