Background.
CD4
+
T cell help is critical in maintaining antiviral immune responses and such help has been shown to be
sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4
+
T cell helper responses appear to be
absent or short-lived, using functional assays.
Methodology/Principal Findings.
Here we used a novel HLA-DR1 tetramer
containing a highly targeted CD4
+
T cell epitope from the hepatitis C virus non-structural protein 4 to track number and
phenotype of hepatitis C virus specific CD4
+
T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in
comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with
acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4
+
T cells. Among patients who transiently controlled
virus replication we observed loss of function, and/or physical deletion of tetramer
+
CD4
+
T cells before viral recrudescence. In
some patients with chronic hepatitis C very low numbers of tetramer
+
cells were detectable in peripheral blood, compared to
robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4
+
T cell
epitope in patients with evolving chronic hepatitis C.
Conclusions/Significance.
During acute hepatitis C a CD4
+
T cell
response against this epitope is readily induced in most, if not all, HLA-DR1
+
patients. This antiviral T cell population becomes
functionally impaired or is deleted early in the course of disease in those where viremia persists.