Seigo Terawaki    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Molecular and Genetic Medicine,    Position   Assistant Professor with Special Assignment
Article types	原著
Language	English
Peer review	Peer reviewed
Title	IFN-α directly promotes programmed cell death-1 transcription and limits the duration of T cell-mediated immunity.
Journal	Formal name：Journal of immunology (Baltimore, Md. : 1950) Abbreviation：J Immunol ISSN code：15506606/00221767
Domestic / Foregin	Foregin
Volume, Issue, Page	186(5),pp.2772-2279
Author and coauthor	Terawaki Seigo, Chikuma Shunsuke, Shibayama Shiro, Hayashi Tamon, Yoshida Takao, Okazaki Taku, Honjo Tasuku
Authorship	Lead author
Publication date	2011/03
Summary	Programmed cell death-1 (PD-1) is an inhibitory coreceptor for T lymphocytes that provides feedback inhibition of T cell activation. Although PD-1's expression on T cells is known to be activation dependent, the factors that determine the timing, intensity, and duration of PD-1 expression in immune reactions are not fully understood. To address this question, we performed a fine mapping analysis of a conserved 5'-flanking region of the PD-1 gene and identified a putative IFN stimulation response element, which was responsible for PD-1 transcription in the 2B4.11 T cell line. Consistent with this finding, activation by IFN-α enhanced both the induction and maintenance of PD-1 expression on TCR-engaged primary mouse T cells through an association IFN-responsive factor 9 (IRF9) to the IFN stimulation response element. Furthermore, PD-1 expression on Ag-specific CD8(+) T cells was augmented by IFN-α in vivo. We propose that strong innate inflammatory responses promote primary T cell activation and their differentiation into effector cells, but also cause an attenuated T cell response in sustained immune reactions, at least partially through type I IFN-mediated PD-1 transcription. Based on this idea, we demonstrate that IFN-α administration in combination with PD-1 blockade in tumor-bearing mice effectively augments the antitumor immunity, and we propose this as a novel and rational approach for cancer immunotherapy.
DOI	10.4049/jimmunol.1003208
PMID	21263073