title: Thymosin-alpha1 increases intrahepatic NKT cells and CTLs in patients with chronic hepatitis B.
abstract: BACKGROUND AND AIM: Thymosin-alpha1 (T-alpha1) influences T-cell maturation, production of Th1-type cytokines, and activity of NK cell-mediated cytotoxicity. The aim of this study is to evaluate the types of lymphocytes that contribute to the reduction in viral load in patients with chronic hepatitis B (CHB) following T-alpha1 treatment. METHODS: Seven patients with CHB were treated with 1.2 mg of T-alpha1 for 24 weeks. Peripheral blood lymphocytes (PBL) and intrahepatic lymphocytes were analyzed by flow cytometry. Serum cytokines (IL-4 and IFN-gamma) were measured by ELISA. RESULTS: Forty-eight weeks after T-alpha1 treatment, two patients (28.6%) showed normalized alanine aminotransferase and decreased HBV-DNA to undetectable level from serum. The histology activity index score significantly decreased (P<0.05). Although elevated serum interferon (IFN)-gamma was not observed, IFN-gamma producing Th1-type CD4(+) PBL appeared to be increased. CD56(+) natural killer T (NKT) cells in PBL did not increase, these cells in the liver remained significantly augmented even at the end of treatment (P<0.05). CD57(+) NKT cells slightly increased and the ratio of CD4(+) T/CD8(+) T cells decreased in the liver. T-alpha1 did not influence either double-positive CD4(+)8(+) T or double-negative CD4(-)8(-) cell subsets. CONCLUSION: NKT cells and CD8(+) cytotoxic T lymphocytes augmented in the liver by T-alpha1 may eliminate hepatitis B virus infected hepatocytes.
authors.affiliation: Department of Internal Medicine III, Niigata University School of Medicine, 951-8122, Niigata, Japan
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sugahara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ichida
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamagiwa
authors.forename: Toru
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Uehara
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Xiu Hua
authors.initials: XH
authors.lastname: Yang
authors.forename: Minoru
authors.initials: M
authors.lastname: Nomoto
authors.forename: Hisami
authors.initials: H
authors.lastname: Watanabe
authors.forename: Toru
authors.initials: T
authors.lastname: Abo
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Asakura