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PMID: 10792025 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 10 ·2000-05-09 ·Pages 5498-503

Takeda K, Hayakawa Y, Van Kaer L, Matsuda H, Yagita H, Okumura K

Abstract

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-deficient gld mice, 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, sensitized gld mice 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.

MeSH Terms
Adoptive Transfer Alanine Transaminase/blood Animals Antigens, CD1/genetics,immunology Apoptosis Aspartate Aminotransferases/blood Concanavalin A Cytotoxicity, Immunologic Fas Ligand Protein Hepatitis, Animal/chemically induced,immunology,pathology Humans Killer Cells, Natural/immunology Liver/immunology,pathology Lymphocyte Transfusion Male Membrane Glycoproteins/deficiency,genetics,immunology Mice Mice, Inbred C57BL Mice, Knockout
Chemicals
Antigens, CD1 FASLG protein, human Fas Ligand Protein Fasl protein, mouse Membrane Glycoproteins Concanavalin A Aspartate Aminotransferases Alanine Transaminase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Takeda K
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan. ktakeda@med.juntendo.ac.jp
Hayakawa Y
Van Kaer L
Matsuda H
Yagita H
Okumura K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.040566697
Email
ktakeda@med.juntendo.ac.jp
Published
2000-05-09
Pages
5498-503
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC25857
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.040566697 PMC Full Text View journal details
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