Role of Vα14+ NKT cells in the development of Hepatitis B virus-specific CTL: Activation of Vα14+ NKT cells promotes the breakage of CTL tolerance

Hiroyasu Ito, Kazuki Ando, Tetsuya Ishikawa, Toshinori Nakayama, Masaru Taniguchi, Kuniaki Saito, Michio Imawari, Hisataka Moriwaki, Takashi Yokochi, Shinichi Kakumu, Mitsuru Seishima

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Abstract

CTLs are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus (HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. In the present study, we found that alpha-galactosylceramide (α-GalCer), a ligand for Vα14-positive NKT cells, strongly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HBsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HBsAg or α-GalCer alone failed to induce HBsAg-specific CTLs, but they were induced by co-administration of both compounds. Furthermore, by limiting dilution analysis, we confirmed the existence of HBsAg-specific CTL precursors in the HBsAg transgenic mice immunized with HBsAg and α-GalCer. A blocking experiment using antibodies to cytokines and CD40 ligand showed that IL-2 and CD40-CD40L interaction mediate the enhancement of CTL induction caused by α-GalCer through NKT cell activation. Our results may open up a new method for clearing the virus from patients with persistent HBV infection.

Original languageEnglish
Pages (from-to)869-879
Number of pages11
JournalInternational Immunology
Volume20
Issue number7
DOIs
Publication statusPublished - 07-2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Ito, H., Ando, K., Ishikawa, T., Nakayama, T., Taniguchi, M., Saito, K., Imawari, M., Moriwaki, H., Yokochi, T., Kakumu, S., & Seishima, M. (2008). Role of Vα14+ NKT cells in the development of Hepatitis B virus-specific CTL: Activation of Vα14+ NKT cells promotes the breakage of CTL tolerance. International Immunology, 20(7), 869-879. https://doi.org/10.1093/intimm/dxn046