Decrease in hepatic CD56(+) T cells and V alpha 24(+) natural killer T cells in chronic hepatitis C viral infection.
OBJECTIVE
The intrahepatic immune system is likely to play a key role in determining the outcome of hepatitis C virus (HCV) infection. The hepatic lymphocyte repertoire is characterised by high CD8/CD4 T cell ratios and large numbers of gamma delta T cells, natural killer (NK) cells, NK T cells and NK receptor-positive T cells. It is not known which of these populations contribute to immunity against HCV or immune pathology.


METHODS
To explore the relative contributions of lymphocyte subpopulations, we have compared the intrahepatic lymphocyte repertoires and cytokine expression in 13 patients with mild chronic hepatitis C infection, 14 with end-stage hepatitis C cirrhosis and five histologically normal livers by flow cytometry and immunohistochemistry.


RESULTS
CD4(+) T cells bearing alpha beta T cell receptors (TCR) were significantly expanded in livers with chronic HCV infection while CD56(+) alpha beta T cells and V alpha 24 TCR-positive T cells were significantly depleted. Expanded CD4(+)T cells were predominantly Th1 cells, producing interferon-gamma but not interleukin-4.


CONCLUSIONS
Failure to resolve HCV infection may be due to deficient innate and/or memory immune responses, while Th1 cells may mediate immune pathology.
Deignan
Tina
T
Education and Research Centre, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Curry
Michael P
MP
Doherty
Derek G
DG
Golden-Mason
Lucy
L
Volkov
Yuri
Y
Norris
Suzanne
S
Nolan
Niamh
N
Traynor
Oscar
O
McEntee
Gerry
G
Hegarty
John E
JE
O'Farrelly
Cliona
C
D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry / Q000166:cytology*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D018417:Th1 Cells / Q000737:chemistry / Q000166:cytology*
D019002:CD56 Antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta