CD8+ T lymphocyte responses are induced during acute hepatitis C virus infection but are not sustained

Abstract

Cellular immune responses are likely to play a key role in determining the clinical outcome in acute infection with hepatitis C virus (HCV), but the dynamics of such responses and their relationship to viral clearance are poorly understood. In a previous study we have shown highly activated, multispecific cytotoxic T lymphocyte responses arising early and persisting in an individual who subsequently cleared the virus. In this study the HCV‐specific CD8+ lymphocytes response has been similarly analyzed, using peptide‐HLA class I tetramers, in a further nine individuals with documented acute HCV infection, six of whom failed to clear the virus. Significant populations of virus‐specific CD8+ lymphocytes were detected at the peak of acute hepatic illness (maximally 3.5 % of CD8+ lymphocytes). Frequencies were commonly lower than those seen previously and were generally not sustained. Early HCV‐specific CD8+ lymphocytes showed an activated phenotype in all patients (CD38+ and HLA class II+), but this activation was short‐lived. Failure to sustain sufficient numbers of activated virus‐specific CD8+ lymphocytes may contribute to persistence of HCV.

Cellular immune responses against hepatitis C virus: the evidence base 2002

“…Work using tetramers derived from HLA-B8 and -B7 restricted peptides has given similar results to A2-based tetramers, i.e. most persistently infected patients show weak or absent responses [9,62]. Table 2 shows the variability of some of these epitopes, dependent on viral genotype.…”

“…The level of ALT may be 500-2000 IU/l, compared with HBV where it may be 5 or 10 times higher [8][9][10].…”

“…The level of activation of HCV-specific T cell responses (assessed by CD38 expression) correlates with the degree of liver inflammation analysed by blood ALT levels [9].…”

“…The picture with regards to CD8 + T cell responses is even less clear. CD8 + T cell responses have been observed in the acute phase of infection in those who fail to clear virus at levels of 1-3% of CD8 + lymphocytes against 1-2 separate T cell epitopes [7,9]. Whether these are the main epitopes targeted in these individuals and how, overall, the responses differ in magnitude between clearers and nonclearers is not known.…”

“…Whether these are the main epitopes targeted in these individuals and how, overall, the responses differ in magnitude between clearers and nonclearers is not known. It appears that failure to clear virus is not due to failure to mount any CTL response whatsoever, although, like CD4 + T cell responses, these may be poorly maintained in the face of ongoing viraemia [9]. The overall quality of the response may differ in terms of magnitude or breadth -or, importantly, peptide selection.…”