期刊
IMMUNOLOGY
卷 142, 期 4, 页码 614-623出版社
WILEY-BLACKWELL
DOI: 10.1111/imm.12274
关键词
3-dioxygenase; cytotoxic T lymphocyte; hepatitis B virus. indoleamine 2; vaccination
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [24659361]
- Grants-in-Aid for Scientific Research [24659361, 23390149] Funding Source: KAKEN
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 alpha-galactosylceramide (alpha-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 alpha-GalCer. The administration of HBsAg and alpha-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, alpha-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.
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