Critical contribution of liver natural killer T cells to a murine model of hepatitis

• DOI: 10.1073/pnas.040566697
• Publication Date: 2002-07-26T14:31:44Z
• Authors: Kazuyoshi Takeda; Yoshihiro Hayakawa; Luc Van Kaer; Hironori Matsuda; Hideo Yagita; Ko Okumura
• Keywords: Cytotoxicity, Immunologic; Male; Mice, Knockout; Fas Ligand Protein; Membrane Glycoproteins; Alanine Transaminase; Apoptosis; Hepatitis, Animal; Adoptive Transfer; 3. Good health; Antigens, CD1; Killer Cells, Natural; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Liver; Lymphocyte Transfusion; Concanavalin A; Animals; Humans; Aspartate Aminotransferases

Natural killer T (NKT) cells constitute a distinct subpopulation of T cells with a unique antigen specificity, prompt effector functions, and an unusual tissue distribution. NKT cells are especially abundant in the liver, but their physiological function in this organ remains unclear. In the present study, we examined the possible contribution of NKT cells to a murine model of hepatitis induced by i.v. injection of Con A. CD1-deficient mice lacking NKT cells were highly resistant to Con A-induced hepatitis. Adoptive transfer of hepatic NKT cells isolated from wild-type mice, but not from FasL-deficientgldmice, sensitized CD1-deficient mice to Con A-induced hepatitis. Furthermore, adoptive transfer of hepatic mononuclear cells from wild-type mice, but not from CD1-deficient mice, sensitizedgldmice to Con A-induced hepatitis. Upon Con A administration, hepatic NKT cells rapidly up-regulated cell surface FasL expression and FasL-mediated cytotoxicity. At the same time, NKT cells underwent apoptosis leading to their rapid disappearance in the liver. These results implicated FasL expression on liver NKT cells in the pathogenesis of Con A-induced hepatitis, suggesting a similar pathogenic role in human liver diseases such as autoimmune hepatitis.