HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy.

Chun Kyon Lee, KwangHyub Han, Jeong Hun Suh, Young Suk Cho, Sun Young Won, Chae Yoon Chon, Young Myoung Moon, In Suh Park

Research output: Contribution to journalArticle

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Abstract

BACKGROUND/AIMS: 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.

Original languageEnglish
Pages (from-to)34-42
Number of pages9
JournalThe Korean journal of hepatology
Volume11
Issue number1
Publication statusPublished - 2005 Jan 1

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Lamivudine
Hepatitis B e Antigens
Hepatitis B virus
T-Lymphocytes
Therapeutics
Viral Load
Recurrence
HLA-A2 Antigen
Seroconversion
Peptides
Viral Antigens
DNA
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Lee, C. K., Han, K., Suh, J. H., Cho, Y. S., Won, S. Y., Chon, C. Y., ... Park, I. S. (2005). HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy. The Korean journal of hepatology, 11(1), 34-42.
Lee, Chun Kyon ; Han, KwangHyub ; Suh, Jeong Hun ; Cho, Young Suk ; Won, Sun Young ; Chon, Chae Yoon ; Moon, Young Myoung ; Park, In Suh. / HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy. In: The Korean journal of hepatology. 2005 ; Vol. 11, No. 1. pp. 34-42.
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title = "HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy.",
abstract = "BACKGROUND/AIMS: 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.",
author = "Lee, {Chun Kyon} and KwangHyub Han and Suh, {Jeong Hun} and Cho, {Young Suk} and Won, {Sun Young} and Chon, {Chae Yoon} and Moon, {Young Myoung} and Park, {In Suh}",
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Lee, CK, Han, K, Suh, JH, Cho, YS, Won, SY, Chon, CY, Moon, YM & Park, IS 2005, 'HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy.', The Korean journal of hepatology, vol. 11, no. 1, pp. 34-42.

HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy. / Lee, Chun Kyon; Han, KwangHyub; Suh, Jeong Hun; Cho, Young Suk; Won, Sun Young; Chon, Chae Yoon; Moon, Young Myoung; Park, In Suh.

In: The Korean journal of hepatology, Vol. 11, No. 1, 01.01.2005, p. 34-42.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HBV-specific CD8+ T cells for sustained HBeAg seroconversion after lamivudine therapy.

AU - Lee, Chun Kyon

AU - Han, KwangHyub

AU - Suh, Jeong Hun

AU - Cho, Young Suk

AU - Won, Sun Young

AU - Chon, Chae Yoon

AU - Moon, Young Myoung

AU - Park, In Suh

PY - 2005/1/1

Y1 - 2005/1/1

N2 - BACKGROUND/AIMS: 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.

AB - BACKGROUND/AIMS: 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.

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