The Role of CD4 and CD8 T-Cells in Spontaneous Clearance of Hepatitis C Virus

About 20%-25% of acutely infected people naturally clear the hepatitis C virus (HCV) without treatment, while the remainder develop chronic infection. The factors that promote spontaneous HCV clearance are not well understood, but timely, efficient, and coordinated activation of both CD4 and CD8 T-cell subsets is thought to be essential for controlling the virus.

As reported in the June 2006 issue of Hepatology, researchers analyzed the breadth, vigor, and quality of CD4 and CD8 T-cell responses simultaneously with panels of peptides covering the entire HCV sequence or containing the HLA-A2 binding motif, and with recombinant HCV proteins in 16 patients with acute HCV infection. They used various techniques including tetramer staining, ELISPOT, and intracellular cytokine staining for interferon gamma, interleukin-2 (IL-2), IL-4, and IL-10.

Results

At clinical onset, CD8 cell responses were similarly weak and narrowly focused in patients with both self-limited (spontaneously cleared) and chronic HCV infection.

At this stage, CD4 cell responses were heavily impaired in patients who went on to develop chronic infection.

Patients who developed chronic infection exhibited weak and narrowly focused CD4 responses, while those who cleared HCV showed strong and broad Th-1 CD4 responses.

Only patients who eventually cleared HCV showed evidence of a mature CD8 cell memory response, sustained by progressive expansion of CD127+ CD8 cells.

Conclusion

The authors concluded that a poor CD8 T-cell response during the acute stage of HCV infection appears to be associated with chronic viral persistence. They added that, "the presence of functional CD4 responses represents one of the factors dictating the fate of infection by directly contributing to control of the virus and by promoting maturation of protective memory CD8 responses."

07/7/06

Reference
S Urbani, B Amadei, P Fisicaro, and others. Outcome of Acute Hepatitis C is Related to Virus-Specific CD4 Function and Maturation of Antiviral Memory CD8 Responses. Hepatology 44(1): 126-139. July 2006.