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

研究成果: Article

34 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)869-879
ページ数11
ジャーナルInternational Immunology
20
発行部数7
DOI
出版物ステータスPublished - 01-07-2008
外部発表Yes

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Natural Killer T-Cells
Hepatitis B Surface Antigens
Hepatitis B virus
CD40 Ligand
Virus Diseases
Transgenic Mice
Hepatitis B Antigens
Viruses
Interleukin-2
Cytokines
Ligands
Antigens
Antibodies
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

これを引用

Ito, Hiroyasu ; Ando, Kazuki ; Ishikawa, Tetsuya ; Nakayama, Toshinori ; Taniguchi, Masaru ; Saito, Kuniaki ; Imawari, Michio ; Moriwaki, Hisataka ; Yokochi, Takashi ; Kakumu, Shinichi ; Seishima, Mitsuru. / 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. 2008 ; 巻 20, 番号 7. pp. 869-879.
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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.",
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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, 巻. 20, 番号 7, pp. 869-879. https://doi.org/10.1093/intimm/dxn046

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

:: International Immunology, 巻 20, 番号 7, 01.07.2008, p. 869-879.

研究成果: Article

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T1 - Role of Vα14+ NKT cells in the development of Hepatitis B virus-specific CTL

T2 - Activation of Vα14+ NKT cells promotes the breakage of CTL tolerance

AU - Ito, Hiroyasu

AU - Ando, Kazuki

AU - Ishikawa, Tetsuya

AU - Nakayama, Toshinori

AU - Taniguchi, Masaru

AU - Saito, Kuniaki

AU - Imawari, Michio

AU - Moriwaki, Hisataka

AU - Yokochi, Takashi

AU - Kakumu, Shinichi

AU - Seishima, Mitsuru

PY - 2008/7/1

Y1 - 2008/7/1

N2 - 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.

AB - 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.

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