Transient restoration of anti-viral T cell responses induced by lamivudine therapy in chronic hepatitis B

被引:246
作者
Boni, C
Penna, A
Bertoletti, A
Lamonaca, V
Rapti, I
Missale, G
Pilli, M
Urbani, S
Cavalli, A
Cerioni, S
Panebianco, R
Jenkins, J
Ferrari, C
机构
[1] Azienda Ospedaliera Parma, Div Malattie Infett & Epatol, I-43100 Parma, Italy
[2] UCL, Inst Hepatol, London WC1E 6BT, England
[3] GlaxoSmithKline Inc, Verona, Italy
[4] GlaxoSmithKline Inc, Upper Providence, PA USA
关键词
chronic hepatitis B; CD4; cells; CD8; lamivudine; cytokine production; T cell cytotoxicity; viral load;
D O I
10.1016/S0168-8278(03)00292-7
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: Lamivudine therapy in patients with chronic hepatitis B can induce the recovery of antiviral T cell responses. It is unknown whether the recovery of T cell responsiveness is long-lasting and persists throughout the treatment and whether the elevation of viremia which follows therapy withdrawal can restore a condition of T cell unresponsiveness. Methods: Frequency and function of circulating hepatitis B virus (HBV)-specific CD4 and CD8 cells from 12 hepatitis e surface antigen + patients with chronic hepatitis B were studied longitudinally before, during and after lamivudine therapy by intracellular cytokine staining, proliferation and cytotoxicity assays against HBV proteins and peptides. CD4-mediated responses were analyzed in all patients, whereas CD8 cells were studied in 6 HLA-A2+ patients. Results: HBV-specific CD4 and CD8 reactivity showed a bi-phasic behavior under lamivudine therapy with an early enhancement of T cell frequency and intensity of responses followed by a persistent decline starting from the 5th to 6th month of treatment. Conclusions: Since restoration of HBV-specific T cell reactivity is only transient, our study indicates that therapeutic stimulation of HBV-specific T cell responses to complement lamivudine treatment should be done early after the initiation of lamivudine. Moreover, the transient nature of the immune reconstitution may represent a favorable condition for virus reactivation once lamivudine therapy is withdrawn. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:595 / 605
页数:11
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