Peripheral virus-specific T-cell interleukin-10 responses develop early in acute hepatitis C infection and become dominant in chronic hepatitis.
OBJECTIVE
Interleukin-10 (IL-10) has been ascribed pro-viral but anti-fibrotic properties in chronic hepatitis C virus (HCV) infection. In this study, we examined the role of HCV-specific T-cell IL-10 response in patients with acute and chronic HCV infection.


METHODS
Peripheral HCV-specific T-cell IL-10 and IFNgamma responses were measured in cytokine Elispot assay using overlapping HCV-derived peptides in patients with chronic (n=61), resolved (n=15) and acute (n=8) hepatitis C, looking for their onset, quantity, breadth and durability relative to clinical and virological outcomes. The source and effect of HCV-specific IL-10 response were determined in depletion and IL-10 neutralization experiments.


RESULTS
Both HCV-specific IL-10 and IFNgamma responses were detected early within 1-2 months of acute clinical hepatitis C. However, only HCV-specific IL-10 response correlated with elevated liver enzymes, increased viremia and suppressed HCV-specific CD4(+) T-cell proliferation in acute infection. While these associations were lost in established chronic infection, HCV-specific IL-10 responses were increased in patients without cirrhosis while IL-10 blockade enhanced antiviral effector IFNgamma responses.


CONCLUSIONS
HCV-specific IL-10 Tr1 responses may play a dual role in HCV infection, dampening effector T-cells to promote viral persistence in acute infection but also protecting against progressive fibrosis in chronic infection.
Kaplan
David E
DE
Research Section, Philadelphia VA Medical Center, Research A216, 3900 Woodland Avenue, Philadelphia, PA 19104, USA. dakaplan@mail.med.upenn.edu
Ikeda
Fusao
F
Li
Yun
Y
Nakamoto
Nobuhiro
N
Ganesan
Sutharsan
S
Valiga
Mary E
ME
Nunes
Frederick A
FA
Rajender Reddy
K
K
Chang
Kyong-Mi
KM
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006526:Hepatitis C / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053701:Receptors, Interleukin-10 / Q000378:metabolism
D053701:Receptors, Interleukin-10; D016753:Interleukin-10; D007371:Interferon-gamma