Characterization of virus-specific T-cell immunity in liver allograft recipients with HCV-induced cirrhosis.
Recurrent hepatitis C infection (HCV) following liver transplantation causes accelerated allograft cirrhosis. Here we characterized HCV-specific immunity in adult liver transplant recipients (n = 74) with and without allograft cirrhosis. Patients were divided into hepatic inflammation/no cirrhosis (METAVIR scores 0-2, HIN) and hepatic cirrhosis (score 3-4, HFC). As control, 20 normal subjects and 10 non-HCV liver transplant patients were included. Twenty-five different serum cytokines were analyzed using LUMINEX. Frequency of T-cells specific to HCV-derived proteins (NS3, NS4, NS5, Core) was characterized using ELISPOT immunoassays. There was no difference in clinical characteristics between HIN (n = 49) and HFC (n = 25) groups. HIN group had high serum IFN-gamma and IL-12 while HFC demonstrated elevated IL-4, IL-5 and IL-10 (p < 0.01). HCV (NS3, NS4, NS5, Core)-specific IFN-gamma-producing CD4+ T-cells were elevated in the HIN group whereas the HFC patients showed predominance of HCV-specific IL-5 and IL-10-producing CD4+ T-cells.


CONCLUSIONS
Lack of HCV-specific Th1-type T-cell immunity is observed in liver transplant recipients with advanced allograft cirrhosis.
Bharat
A
A
Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Barros
F
F
Narayanan
K
K
Borg
B
B
Lisker-Melman
M
M
Shenoy
S
S
Lowell
J
J
Crippin
J
J
Chapman
W
W
Mohanakumar
T
T
D000328:Adult; D016207:Cytokines / Q000097:blood; D005260:Female; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008103:Liver Cirrhosis / Q000097:blood / Q000276:immunology / Q000821:virology*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D016207:Cytokines