Mechanism of restoration of immune responses of patients with chronic hepatitis B during lamivudine therapy: increased antigen processing and presentation by dendritic cells.
Restoration of host immunity has been reported in patients with chronic hepatitis B (CHB) after treatment with lamivudine; however, the underlying mechanisms of this treatment have not been determined. This study examined the role of antigen-presenting dendritic cells (DC) in restoration of host immunity. Circulating DC were isolated from peripheral blood of 23 patients with CHB before and 1, 3, and 12 months after starting lamivudine therapy. The non-antigen-specific proliferation of DC was assessed in allogenic mixed leucocyte reaction. Dendritic cells were cultured with hepatitis B surface antigen (HBsAg) to prepare HBsAg-pulsed DC. Proliferative capacity and production of interleukin (IL)-12 and interferon (IFN)-γ of HBsAg-pulsed DC were evaluated. Circulating unpulsed DC and HBsAg-pulsed DC showed significantly higher levels of T-cell proliferation capacities 1 month after lamivudine therapy compared to proliferation levels before therapy (P<0.05). HBsAg-pulsed DC also produced significantly higher levels of IL-12 and IFN-γ with lamivudine therapy compared to levels before therapy (P<0.05). HBsAg-pulsed DC from lamivudine-treated patients induced proliferation of T cells of patients with CHB in an antigen-specific manner (P<0.05). However, T-cell stimulatory capacity of DC did not increase significantly 3 and 12 months after lamivudine therapy compared to 1 month after lamivudine therapy. Immune restoration as a result of lamivudine therapy is regulated at least in part by activation of DC. However, progressive activation of DC was not seen as treatment duration progressed, indicating the limitations of this mechanism of viral clearance.
Akbar
S M F
SM
Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan. sheikh.akbar@po.toshiba.co.jp
Horiike
N
N
Chen
S
S
Michitaka
K
K
Abe
M
M
Hiasa
Y
Y
Matsuura
B
B
Onji
M
M
D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D048708:Cell Growth Processes / Q000276:immunology; D004279:DNA, Viral / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D016130:Immunophenotyping; D019259:Lamivudine / Q000008:administration & dosage*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D018709:Statistics, Nonparametric; D055815:Young Adult
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine