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

被引：50

作者：

Ito, Hiroyasu ^{[1
,2
]}

Ando, Kazuki ^{[1
,3
]}

Ishikawa, Tetsuya ^{[4
]}

Nakayama, Toshinori ^{[5
]}

Taniguchi, Masaru ^{[6
]}

Saito, Kuniaki ^{[1
,7
,8
]}

Imawari, Michio ^{[9
]}

Moriwaki, Hisataka ^{[10
]}

Yokochi, Takashi ^{[2
]}

Kakumu, Shinichi ^{[11
]}

Seishima, Mitsuru ^{[1
]}

机构：

[1] Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 5011194, Japan

[2] Aichi Med Univ, Dept Microbiol & Immunol, Nagakute, Aichi 4801195, Japan

[3] Goto Clin, Gifu 5030899, Japan

[4] Nagoya Kyoritsu Hosp, Canc Immunotherapy Ctr, Nagoya, Aichi 4540933, Japan

[5] Chiba Univ, Grad Sch Med, Dept Immunol, Chuo Ku, Chiba 2608670, Japan

[6] RIKEN, Yokohama Inst, Res Ctr Allergy & Immunol, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[7] Kyoto Univ, Grad Sch Med, Kyoto 6068507, Japan

[8] Kyoto Univ, Fac Med, Kyoto 6068507, Japan

[9] Showa Univ, Sch Med, Dept Internal Med 2, Tokyo 1428666, Japan

[10] Gifu Univ, Grad Sch Med, Dept Internal Med 1, Gifu 5011194, Japan

[11] Aichi Med Univ, Div Gastroenterol, Dept Internal Med, Nagakute, Aichi 4801195, Japan

来源：

INTERNATIONAL IMMUNOLOGY | 2008年 / 20卷 / 07期

关键词：

CTL; hepatitis B virus; NKT cell;

D O I：

10.1093/intimm/dxn046

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 [免疫学];

摘要：

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 (alpha-GalCer), a ligand for V alpha 14-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 alpha-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 alpha-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 alpha-GalCer through NKT cell activation. Our results may open up a new method for clearing the virus from patients with persistent HBV infection.

引用

页码：869 / 879

页数：11

共 42 条

[1]

MECHANISMS OF CLASS-I RESTRICTED IMMUNOPATHOLOGY - A TRANSGENIC MOUSE MODEL OF FULMINANT-HEPATITIS [J].