Fukushima J. Med. Sci.
Vol. 48, No. 2, 2002

［Regular Papers］

HLA-A2-RESTRICTED CYTOTOXIC T LYMPHOCYTE ACTIVITY
DURING INTERFERON BETA THERAPY IN PATIENTS
WITH CHRONIC HEPATITIS C

HIROMASA OHIRA¹⁾, MASAHIRO IWASAKI²⁾, JUNKO TAKIGUCHI¹⁾,
TSUYOSHI RAI¹⁾, SHOICHIRO SHISHIDO¹⁾, KAZUMICHI ABE¹⁾,
JUNKO TAKEDA¹⁾, JUN TOJO¹⁾, YUKIO SATO¹⁾ and REIJI KASUKAWA¹⁾

¹⁾Department of Internal Medicine II, Fukushima Medical University School of Medicine
²⁾R&D Center, BML

(Received March 27, 2002, accepted May 29, 2002)

Abstract: Background and Aims : Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) may contribute to viral clearance and liver cell injury in patients with chronic hepatitis C. In the present study, we attempted to determine the serial HCV-specific CTL activity during interferon-beta (IFN-β) therapy in patients with chronic hepatitis C and whether there is any relationship between the CTL response and clinical response to IFN-β therapy.
Methods : Eight HLA-A2-positive patients with chronic hepatitis C were treated initially with 6 million U/ml of IFN-β every day for 8 weeks and then 3 times weekly for the subsequent 16 weeks. Peripheral blood mononuclear cells (PBMC) were collected before the start, 4 weeks after the start, and after the end of IFN treatment and were stimulated with 2 peptides corresponding to core sequences, which were previously reported to have an HLA-A2 restricted-CTL epitopes. Cytolytic activity was determined by a standard ⁵¹Cr-release assay using allogenic HLA-matched EBV-transformed B lymphoblastoid cell lines (B-LCL).
Results : HCV-specific CTL responses were detected in 2 of the 8 patients before treatment with IFN-β. One of 2 patients was not observed HCV-specific CTL responses after 4 weeks of IFN-β treatment, however these two patients showed CTL responses at the end of IFN-β treatment, and finally HCV-RNA was negative. In addition, HCV-specific CTL responses were observed in 4 patients after 4 weeks of IFN-β treatment. Three of these 4 patients showed CTL responses only at 4 weeks after IFN-β treatment. However, there were no differences between clinical parameters or between IFN efficacy in HCV-specific CTL response-positive (n＝4) and -negative (n＝4) patients at 4 weeks after the start of IFN-β treatment.
Conclusions : These findings suggest that there are few relations between peripheral HCV-specific CTL response and clinical response to IFN therapy in patients with chronic hepatitis C, although IFN enhances the host immune response against HCV synergistically with antiviral activities.

Key words: chronic hepatitis C, cytotoxic T lymphocyte, interferon, host immune response, target cell

大平弘正，岩崎匡洋，滝口純子，雷 毅，宍戸昌一郎，阿部和道，武田順子，東條 淳，佐藤由紀夫，粕川禮司

Reprint requests to: Hiromasa Ohira, Department of Internal Medicine II, Fukushima Medical University School of Medicine, Fukushima City 960-1295, Japan.