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Induction of hepatitis B virus surface antigen‐specific cytotoxic T lymphocytes can be up‐regulated by the inhibition of indoleamine 2, 3‐dioxygenase activity
Author(s) -
Ito Hiroyasu,
Ando Tatsuya,
Ando Kazuki,
Ishikawa Tetsuya,
Saito Kuniaki,
Moriwaki Hisataka,
Seishima Mitsuru
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12274
Subject(s) - ctl* , cytotoxic t cell , immunology , indoleamine 2,3 dioxygenase , hepatitis b virus , virology , antigen , virus , medicine , biology , cd8 , in vitro , tryptophan , biochemistry , amino acid
Summary Cytotoxic T lymphocytes ( CTL s) 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 CTL s 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 ( HB sAg)‐specific CTL s. In the present study, we found that inhibition of indoleamine 2,3‐dioxygenase ( IDO ) activity enhanced the induction of HB sAg‐specific CTL s after immunization with HB sAg and α ‐GalCer. The administration of HB sAg and α ‐GalCer increased the production of interleukin‐2 and interleukin‐12b, which are crucial for the induction of HB sAg‐specific CTL s. 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 CD 11b + cells, and these cells inhibited proliferation of HB sAg‐specific CTL s. Our results lead to strategies for improving the induction of HB sAg‐specific CTL s.