[HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy].
OBJECTIVE
Viral suppression of the hepatitis B virus (HBV) can be induced by lamivudine, but the relapse seen in many patients after cessation of lamivudine therapy is troublesome. We thought that the host immune response is important to prevent viral relapse. We compared the frequency of HBV-specific CD8+ T cells in the peripheral blood and their expansion capacity after exposure to viral antigen between the patients showing sustained HBeAg seroconversion after use of lamivudine and those patients without sustained response.


METHODS
We analyzed HBV-specific CD8+ T cells that were isolated from the blood of 14 patients with HLA-A2 who showed lamivudine induced HBeAg seroconversion (HBV DNA < 0.5 pg/mL, and the cells were negative for HBeAg) at the end of lamivudine therapy. The purified T cells were directly stained ex vivo, after they had been stimulate with synthetic peptide, using the HBV core 18-27-specific HLA tetramer (Tc 18-27) and monoclonal antibody to CD8. The HBV viral load was quantified by the Amplicor HBV Monitor assay.


RESULTS
In patients with a sustained HBeAg response (the sustained group) for a duration of 15.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 49.5 (15-135). On the contrary, in patients who experienced relapse (the relapsed group) during a median of 7.5 months of follow-up, the median number of Tc 18-27 cells out of the 5 X 10(4) CD8+ T cells was 13.5 (0-95). Especially, among patients with a viral load of HBV DNA < 1 X 10(3) copies at the end of treatment, the median number of Tc 18-27 cells out of 5 X 10(4) CD8+ T cells was 87 (45-135) in sustained group compared to 12 (6-50) in the relapsed group. All patients in the sustained group demonstrated a vigorous expansion of the core 18-27-specific CD8+ T cells after stimulation with viral peptide, in contrast to only 3 out of 8 patients in the relapsed group.


CONCLUSIONS
This study demonstrates that the frequency and functional responsiveness of the circulating HBV-specific CD8+ T cells may be important for obtaining a sustained HBeAg response to lamivudine.
Lee
Chun Kyon
CK
Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Koyang, Korea. cklee33@nhimc.or.kr
Han
Kwang-Hyub
KH
Suh
Jeong Hun
JH
Cho
Young Suk
YS
Won
Sun Young
SY
Chon
Chae Yoon
CY
Moon
Young Myoung
YM
Park
In Suh
IS
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D012008:Recurrence; D019562:Viral Load
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D019259:Lamivudine