Analysis of intrahepatic HBV-specific cytotoxic T-cells during and after acute HBV infection in humans.
OBJECTIVE
Characteristics of the intrahepatic virus-specific T-cell response in patients with acute hepatitis B virus (HBV) infection have not been studied due to the risk of complications associated with standard liver biopsies. In this study we aimed to characterize the virus-specific CD8 + T-cell response in the liver of patients with acute HBV infection using fine-needle aspiration-biopsy (FNAB).


METHODS
In HLA-A2 positive patients with acute HBV infection a FNAB was performed at first presentation, at the time of HBsAg-seroconversion and 3 months after HBsAg-seroconversion. HLA-A2 tetramers were used to identify HBV-specific CD8 + T-cells in FNAB-cytology and peripheral blood (PB).


RESULTS
At first presentation there was a correlation between the frequency of intrahepatic CD8 + T-cells and the degree of liver damage. At all time points there was sequestering of HBV-specific CD8 + T-cells in the liver, and the percentage of intrahepatic HLA-DR expressing HBV-specific CD8 + T-cells was higher than in PB. Three months after HBsAg-seroconversion the frequency of intrahepatic HBV-specific CD8 + T-cells remained high.


CONCLUSIONS
HBV-specific CD8 + T-cells are compartmentalized in the liver during acute HBV infection. Their presence in the liver may suggest a role in the resolution of the infection. Intrahepatic HBV-specific CD8 + T cells remain detectable at high frequencies after HBsAg-seroconversion.
Sprengers
Dave
D
Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
van der Molen
Renate G
RG
Kusters
Johannes G
JG
De Man
Robert A
RA
Niesters
Hubert G M
HG
Schalm
Solko W
SW
Janssen
Harry L A
HL
D000208:Acute Disease; D000328:Adult; D044963:Biopsy, Fine-Needle; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology
D004279:DNA, Viral; D006684:HLA-DR Antigens; D006514:Hepatitis B Surface Antigens