title: Induction of rapid T cell death and phagocytic activity by Fas-deficient lpr macrophages.
abstract: Peripheral T cells are maintained by the apoptosis of activated T cells through the Fas-Fas ligand system. Although it is well known that normal T cells fail to survive in the Fas-deficient immune condition, the molecular mechanism for the phenomenon has yet to be elucidated. In this study, we demonstrate that rapid cell death and clearance of normal T cells were induced by Fas-deficient lpr macrophages. Transfer of normal T cells into lpr mice revealed that Fas expression on donor T cells was promptly enhanced through the IFN-γ/IFN-γR. In addition, Fas ligand expression and phagocytic activity of lpr macrophages were promoted through increased NF-κB activation. Controlling Fas expression on macrophages plays an essential role in maintaining T cell homeostasis in the peripheral immune system. Our data suggest a critical implication to the therapeutic strategies such as transplantation and immunotherapy for immune disorder or autoimmunity related to abnormal Fas expression.
authors.affiliation: Department of Oral Molecular Pathology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8504, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Oura
authors.forename: Rieko
authors.initials: R
authors.lastname: Arakaki
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamada
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Naozumi
authors.initials: N
authors.lastname: Ishimaru
mesh_terms: D000818:Animals; D016923:Cell Death / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D056747:Immunomodulation / Q000235:genetics; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019014:fas Receptor / Q000172:deficiency*
chemical_list: D053222:Fas Ligand Protein; D016328:NF-kappa B; D019014:fas Receptor