Induction of hepatitis B virus surface antigen-specific cytotoxic T lymphocytes can be up-regulated by the inhibition of indoleamine 2, 3-dioxygenase activity

Hiroyasu Ito, Tatsuya Ando, Kazuki Ando, Tetsuya Ishikawa, Kuniaki Saito, Hisataka Moriwaki, Mitsuru Seishima

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20 Citations (Scopus)

Abstract

Cytotoxic T lymphocytes (CTLs) are thought to be major effectors involved in viral clearance during acute infections, including hepatitis B virus (HBV) infection. A persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which may be reflective of tolerance to HBV. Efficient induction of HBV-specific CTLs leads to the clearance of HBV in patients with a chronic HBV infection. Previously, we reported that α-galactosylceramide (α-GalCer), a specific natural killer T (NKT) cell agonist, enhanced the induction of HBV surface antigen (HBsAg)-specific CTLs. In the present study, we found that inhibition of indoleamine 2,3-dioxygenase (IDO) activity enhanced the induction of HBsAg-specific CTLs after immunization with HBsAg and α-GalCer. The administration of HBsAg and α-GalCer increased the production of interleukin-2 and interleukin-12b, which are crucial for the induction of HBsAg-specific CTLs. The production of these cytokines was more strongly enhanced in IDO knockout mice compared with wild-type mice. In addition, α-GalCer induced the production of IDO in CD11b+ cells, and these cells inhibited proliferation of HBsAg-specific CTLs. Our results lead to strategies for improving the induction of HBsAg-specific CTLs.

Original languageEnglish
Pages (from-to)614-623
Number of pages10
JournalImmunology
Volume142
Issue number4
DOIs
Publication statusPublished - 08-2014

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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