RRC ID 39795
著者 Kaneko Y, Harada M, Kawano T, Yamashita M, Shibata Y, Gejyo F, Nakayama T, Taniguchi M.
タイトル Augmentation of Valpha14 NKT cell-mediated cytotoxicity by interleukin 4 in an autocrine mechanism resulting in the development of concanavalin A-induced hepatitis.
ジャーナル J Exp Med
Abstract The administration of concanavalin A (Con A) induces a rapid severe injury of hepatocytes in mice. Although the Con A-induced hepatitis is considered to be an experimental model of human autoimmune hepatitis, the precise cellular and molecular mechanisms that induce hepatocyte injury remain unclear. Here, we demonstrate that Valpha14 NKT cells are required and sufficient for induction of this hepatitis. Moreover, interleukin (IL)-4 produced by Con A-activated Valpha14 NKT cells is found to play a crucial role in disease development by augmenting the cytotoxic activity of Valpha14 NKT cells in an autocrine fashion. Indeed, short-term treatment with IL-4 induces an increase in the expression of granzyme B and Fas ligand (L) in Valpha14 NKT cells. Moreover, Valpha14 NKT cells from either perforin knock-out mice or FasL-mutant gld/gld mice fail to induce hepatitis, and hence perforin-granzyme B and FasL appear to be effector molecules in Con A-induced Valpha14 NKT cell-mediated hepatocyte injury.
巻・号 191(1)
ページ 105-14
公開日 2000-1-3
DOI 10.1084/jem.191.1.105
PMID 10620609
PMC PMC2195789
MeSH Adoptive Transfer Animals Antigens / analysis* Antigens, Surface Chemical and Drug Induced Liver Injury / etiology* Concanavalin A / toxicity* Cytotoxicity, Immunologic* Interferon-gamma / physiology Interleukin-4 / physiology* Killer Cells, Natural / physiology* Lectins, C-Type Male Mice Mice, Inbred C57BL NK Cell Lectin-Like Receptor Subfamily B Proteins / analysis* Receptors, Antigen, T-Cell, alpha-beta / analysis*
IF 11.743
引用数 338
WOS 分野 IMMUNOLOGY MEDICINE, RESEARCH & EXPERIMENTAL
リソース情報
ヒト・動物細胞 TLR2(RCB0750)