The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection.
OBJECTIVE
The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial.


METHODS
Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver.


RESULTS
A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage.


CONCLUSIONS
HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.
Freeman
Anthony J
AJ
Viral Hepatitis Research, Gastrointestinal and Liver Unit, The Prince of Wales Hospital, Barker Street, Randwick, Sydney, NSW 2031, Australia. freemanto@sesahs.nsw.gov.au
Pan
Yong
Y
Harvey
Charles E
CE
Post
Jeffrey J
JJ
Law
Matthew G
MG
White
Peter A
PA
Rawlinson
William D
WD
Lloyd
Andrew R
AR
Marinos
George
G
Ffrench
Rosemary A
RA
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D005260:Female; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000473:pathology* / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology*; D019562:Viral Load; D014766:Viremia / Q000821:virology; D014779:Virus Replication
D000410:Alanine Transaminase