Augmentation of Vα14 Nkt Cell–Mediated Cytotoxicity by Interleukin 4 in an Autocrine Mechanism Resulting in the Development of Concanavalin a–Induced Hepatitis

作者：Yoshikatsu Kaneko, Michishige Harada, Tetsu Kawano, Masakatsu Yamashita, Youichi Shibata, Fumitake Gejyo, Toshinori Nakayama, Masaru Taniguchi · 发表于：The Journal of Experimental Medicine · 年份：2000 · DOI：10.1084/jem.191.1.105 · 被引用次数：401 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Endoplasmic Reticulum Stress and Disease

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.