Seigo Terawaki
Department Kawasaki Medical School Kawasaki Medical School, Department of Molecular and Genetic Medicine, Position Assistant Professor with Special Assignment |
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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 |