The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection.
Hepatitis B virus (HBV)-specific T cells play a key role in clearance of the virus and in the pathogenesis of liver disease. Peripheral blood (n = 25) and liver biopsies (n = 19) were collected from individuals with chronic untreated HBV infection. Whole blood, cultured peripheral blood mononuclear cells (PBMCs), and cultured liver-infiltrating lymphocytes (LILs) were each stimulated with an overlapping peptide library to the whole HBV genome. The expression of T helper 1 (Th1) cytokines [interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin 2 (IL-2)] and interleukin 10 (IL-10) was analyzed by intracellular cytokine staining and flow cytometry. In ex vivo whole blood, more lymphocytes produced Th1 cytokines than IL-10. When comparing cultured LILs with cultured PBMCs, we found a significantly higher magnitude of CD8(+) T cells from the liver producing IL-10 (P = 0.044), primarily in hepatitis B e antigen positive (HBeAg(+)) individuals. A positive correlation resulted between the magnitude of HBV-specific TNF-alpha(+) CD4(+) T cells in the liver and the degree of liver inflammation and fibrosis (P = 0.002 and P = 0.006, respectively).


CONCLUSIONS
The differences in cytokine production from HBV-specific T cells in blood and liver may explain the capacity for HBV to persist in the absence of significant hepatic destruction and highlights the balance between cytokine-mediated viral control and liver damage.
Chang
J Judy
JJ
Department of Microbiology and Immunology, University of Melbourne, Australia.
Thompson
Alexander J V
AJ
Visvanathan
Kumar
K
Kent
Stephen J
SJ
Cameron
Paul U
PU
Wightman
Fiona
F
Desmond
Paul
P
Locarnini
Stephen A
SA
Lewin
Sharon R
SR
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism*; D004270:DNA, Circular / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013194:Staining and Labeling; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004270:DNA, Circular; D006513:Hepatitis B e Antigens; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10