Hepatitis B virus-induced defect of monocyte-derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escape.
Dendritic cells (DC) are the most potent antigen-presenting cells and play a central role in the induction of antiviral immune responses. Recently, we have shown that monocyte-derived DC (MoDC) from patients with chronic hepatitis B virus (HBV) infection are functionally impaired. In our present study MoDC from healthy subjects were propagated in vitro and inoculated with HBV particles to investigate the precise mechanisms that underly MoDC dysfunction. T-cell proliferation assays revealed an impaired allostimulatory capacity of HBV-inoculated MoDC (HBV-MoDC) as well as a lower potential of stimulating autologous T cells against a recall antigen in comparison to control-MoDC. Interleukin-2, tumour necrosis factor-alpha and interferon-gamma production by T cells in proliferation assays with HBV-MoDC was significantly lower than with control-MoDC and correlated with lower IL-12 production in HBV-MoDC cultures. The presence of the nucleoside analogue lamivudine (3TC), an inhibitor of HBV replication, restored impaired allostimulatory function of HBV-MoDC and up-regulated major histocompatibility complex class II expression. These results show that HBV infection compromises the antigen-presenting function of MoDC with concomitant impairment of T helper cell type 1 responses. This may play an important role for viral immune escape leading to chronic HBV infection. However, 3TC treatment can overcome HBV-MoDC-related T-cell hyporeactivity and this underscores its important role in enhanced immune responses to HBV.
Beckebaum
Susanne
S
Department of Gastroenterology and Hepatology, Department of General Surgery and Transplantation, and Institute of Immunology, University of Essen, Germany.
Cicinnati
Vito R
VR
Zhang
Xia
X
Ferencik
Stanislav
S
Frilling
Andrea
A
Grosse-Wilde
Hans
H
Broelsch
Christoph Erich
CE
Gerken
Guido
G
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D019259:Lamivudine / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D009000:Monocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D006684:HLA-DR Antigens; D007376:Interleukin-2; D013745:Tetanus Toxoid; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D019259:Lamivudine; D007371:Interferon-gamma